3-叔丁基苯甲醛

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: The title compound was prepared in an analogous manner as described for example 1h, starting from (1S,3R,4S,5S)-3-amino-5-[3-fluoro-4-nitro-5-((R)-2,2,2-trifluoro-1-methoxy-methyl-ethoxy)-benzyl]-1-oxo-tetrahydro-thiopyran-4-ol TFA salt (310 mg, 0.7 mmol) and 3-tert-butyl-benzaldehyde and was obtained after purification by flash-chromatography (hexane-(EtOAc-MeOH 9:1) gradient) as a light yellow foam: TLC (EtOAc-MeOH 9:1) Rf=0.38; HPLC RtH1=1.05 min; ESIMS [M+H]+=591; 1H NMR (600 MHz, CDCl3): δ 7.36 (s, 1H), 7.28 (s, 1H), 7.23 (m, 2H), 7.13 (d, 1H), 7.11 (d, 1H), 5.66 (m, 1H), 5.16 (d, 1H), 3.83-3.79 (m, 2H), 3.69 (dd, 1H), 3.63 (d, 1H), 3.55 (m, 1H), 3.30 (s, 3H), 3.14 (m, 2H), 3.00 (d, 1H), 2.55 (m, 1H), 2.5-2.4 (m, 3H), 1.95 (m, 1H), 1.25 (s, 9H). was obtained after purification by flash-chromatography (hexane-(EtOAc-MeOH 9:1) gradient) as a light yellow foam HPLC RtH1=1.05 min

反应条件: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of (3R,4S,5S)-3-amino-5-[3-fluoro-4-nitro-5-((R)-2,2,2-trifluoro-1-methoxy-methyl-ethoxy)-benzyl]-tetrahydro-thiopyran-4-ol hydrochloride (1.217 g, 2.52 mmol) in MeOH-CH2Cl2 1:2 (28 mL) was added NaOAc (0.517 g, 6.3 mmol), powdered molecular sieves (4A) and 3-tert-butyl-benzaldehyde (CAS registry 23039-28-3) (0.413 g, 2.55 mmol). The reaction mixture was stirred at 25° C. for 16 h, acetic acid (0.5 mL) was added followed by NaBH3CN (0.396 g, 6.3 mmol). The reaction mixture was stirred at room temperature for 3 h and was quenched by adding 2N aq. HCl solution. EtOAc was added and the solution was washed with 2N K2CO3 solution and with brine. The organic phase was dried over Na2SO4, filtered and evaporated. The title compound was obtained after purification by flash-chromatography on NH4OH deactivated silica gel (90 g, toluene-EtOAc 1:1) as a light yellow oil: TLC (toluene-ETA 85:15) Rf=0.52; HPLC RtA=2.178 min; ESIMS [M+H]+=575; 1H NMR (600 MHz, CDCl3): δ 7.33 (s, 1H), 7.28 (s, 1H), 7.26 (m, 2H), 7.18-7.08 (m, 2H), 5.7 (broad, 1H), 5.06 (d, 1H), 3.9-3.78 (m, 2H), 3.71-3.62 (m, 2H), 3.31 (s, 3H), 3.22 (d, 1H), 2.90 (m, 1H), 2.82 (d, 1H), 2.55 (m, 1H), 2.48 (s broad, 1H), 2.41 (m, 1H), 2.35-2.20 (m, 3H), 1.93 (m, 1H), 1.25 (s, 9H). The reaction mixture was stirred at room temperature for 3 h was quenched by adding 2N aq. HCl solution EtOAc was added the solution was washed with 2N K2CO3 solution and with brine The organic phase was dried over Na2SO4 filtered evaporated

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: The title compound was prepared in analogous manner as described for example 1h) from (3R,4S,5S)-3-Amino-5-[4-nitro-3-fluoro-5-(2,2,2-trifluoro-ethoxy)-benzyl]-1,1-dioxo-hexahydro-1lambda*6*-thiopyran-4-ol hydrochloride salt (1.26 g, 2.78 mmol) and 3-tert-butyl benz-aldehyde (0.361 g, 2.26 mmol); ESIMS [M+H]+=563, UPLC RtD=1.576 min, 1H NMR (600 MHz, DMSO-d6): δ 7.35 (s, 1H), 7.27-7.21 (m, 2H), 7.15 (m, 2H), 7.10 (d, 1H), 5.32 (d, 1H), 5.01 (q, 2H), 3.81 (m, 1H), 3.63 (m, 1H), 3.38 (m, 1H), 3.20 (m, 1H), 3.10 (m, 1H), 3.05-2.98 (m, 2H), 2.80 (m, 2H), 2.63 (m, 1H), 2.41 (s, 1H), 2.14 (m, 1H), 1.25 (s, 9H). ESIMS [M+H]+=563, UPLC RtD=1.576 min, 1H NMR (600 MHz, DMSO-d6): δ 7.35 (s, 1H), 7.27-7.21 (m, 2H), 7.15 (m, 2H), 7.10 (d, 1H), 5.32 (d, 1H), 5.01 (q, 2H), 3.81 (m, 1H), 3.63 (m, 1H), 3.38 (m, 1H), 3.20 (m, 1H), 3.10 (m, 1H), 3.05-2.98 (m, 2H), 2.80 (m, 2H), 2.63 (m, 1H), 2.41 (s, 1H), 2.14 (m, 1H), 1.25 (s, 9H)

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of (3R*,4S*,5S*)-3-amino-5-(3-fluoro-4-nitro-benzyl)-1,1-dioxo-hexahydro-1lambda*6*-thiopyran-4-ol hydrochloride (0.14 g, 0.39 mmol) in MeOH-CH2Cl2 1:1 (3 mL) was added NaOAc (0.065 g, 0.78 mmol) and 3-tert-butyl-benzaldehyde (0.07 g, 0.43 mmol). The reaction mixture was stirred at 25° C. for 0.5 h before NaBH3CN (0.039 g, 0.59 mmol) was added followed by stirring for 16 h. The reaction mixture was acidified with 1N aq. HCl, stirred for 15 min, basified with K2CO3-solution and extracted with EtOAc. The combined organic layers were washed with brine, dried over MgSO4 and evaporated. The title compound was obtained after purification by flash-chromatography on silica gel (hexane-CH2Cl2-MeOH 20:20:1 to 1:20:5) as a light yellow foam: TLC (EtOAc) Rf=0.45; HPLC RtA=1.78 min; ESIMS [M+H]+=465; 1H NMR (400 MHz, CDCl3): δ 8.02 (t, 1H), 7.1-7.4 (m, 6H), 4.18 (s, 1H), 3.88 (d, 1H), 3.78 (d, 1H), 3.64 (m, 1H), 3.41 (ddd, 1H), 3.24 (ddd, 1H), 3.12 (dt, 1H), 3.00 (dd, 1H), 2.84, (m, 2H), 2.69 (m, 2H), 2.44 (m, 1H), 1.33 (s, 9H). was added stirred for 15 min extracted with EtOAc The combined organic layers were washed with brine dried over MgSO4 evaporated

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: The title compound was prepared in an analogous manner as described for example 1h, starting from (1S,3R,4S,5S)-3-amino-5-[3-fluoro-4-nitro-5-((R)-2,2,2-trifluoro-1-methoxy-methyl-ethoxy)-benzyl]-1-oxo-tetrahydro-thiopyran-4-ol TFA salt (310 mg, 0.7 mmol) and 3-tert-butyl-benzaldehyde and was obtained after purification by flash-chromatography (hexane-(EtOAc-MeOH 9:1) gradient) as a light yellow foam: TLC (EtOAc-MeOH 9:1) Rf=0.38; HPLC RtH1=1.05 min; ESIMS [M+H]+=591; 1H NMR (600 MHz, CDCl3): δ 7.36 (s, 1H), 7.28 (s, 1H), 7.23 (m, 2H), 7.13 (d, 1H), 7.11 (d, 1H), 5.66 (m, 1H), 5.16 (d, 1H), 3.83-3.79 (m, 2H), 3.69 (dd, 1H), 3.63 (d, 1H), 3.55 (m, 1H), 3.30 (s, 3H), 3.14 (m, 2H), 3.00 (d, 1H), 2.55 (m, 1H), 2.5-2.4 (m, 3H), 1.95 (m, 1H), 1.25 (s, 9H). was obtained after purification by flash-chromatography (hexane-(EtOAc-MeOH 9:1) gradient) as a light yellow foam HPLC RtH1=1.05 min

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: The title compound was prepared in an analogous manner as described for example 1h, starting from (1S,3R,4S,5S)-3-amino-5-[3-fluoro-4-nitro-5-((R)-2,2,2-trifluoro-1-methoxy-methyl-ethoxy)-benzyl]-1-oxo-tetrahydro-thiopyran-4-ol TFA salt (310 mg, 0.7 mmol) and 3-tert-butyl-benzaldehyde and was obtained after purification by flash-chromatography (hexane-(EtOAc-MeOH 9:1) gradient) as a light yellow foam: TLC (EtOAc-MeOH 9:1) Rf=0.38; HPLC RtH1=1.05 min; ESIMS [M+H]+=591; 1H NMR (600 MHz, CDCl3): δ 7.36 (s, 1H), 7.28 (s, 1H), 7.23 (m, 2H), 7.13 (d, 1H), 7.11 (d, 1H), 5.66 (m, 1H), 5.16 (d, 1H), 3.83-3.79 (m, 2H), 3.69 (dd, 1H), 3.63 (d, 1H), 3.55 (m, 1H), 3.30 (s, 3H), 3.14 (m, 2H), 3.00 (d, 1H), 2.55 (m, 1H), 2.5-2.4 (m, 3H), 1.95 (m, 1H), 1.25 (s, 9H). was obtained after purification by flash-chromatography (hexane-(EtOAc-MeOH 9:1) gradient) as a light yellow foam HPLC RtH1=1.05 min

反应条件: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of (3R,4S,5S)-3-amino-5-[3-fluoro-4-nitro-5-((R)-2,2,2-trifluoro-1-methoxy-methyl-ethoxy)-benzyl]-tetrahydro-thiopyran-4-ol hydrochloride (1.217 g, 2.52 mmol) in MeOH-CH2Cl2 1:2 (28 mL) was added NaOAc (0.517 g, 6.3 mmol), powdered molecular sieves (4A) and 3-tert-butyl-benzaldehyde (CAS registry 23039-28-3) (0.413 g, 2.55 mmol). The reaction mixture was stirred at 25° C. for 16 h, acetic acid (0.5 mL) was added followed by NaBH3CN (0.396 g, 6.3 mmol). The reaction mixture was stirred at room temperature for 3 h and was quenched by adding 2N aq. HCl solution. EtOAc was added and the solution was washed with 2N K2CO3 solution and with brine. The organic phase was dried over Na2SO4, filtered and evaporated. The title compound was obtained after purification by flash-chromatography on NH4OH deactivated silica gel (90 g, toluene-EtOAc 1:1) as a light yellow oil: TLC (toluene-ETA 85:15) Rf=0.52; HPLC RtA=2.178 min; ESIMS [M+H]+=575; 1H NMR (600 MHz, CDCl3): δ 7.33 (s, 1H), 7.28 (s, 1H), 7.26 (m, 2H), 7.18-7.08 (m, 2H), 5.7 (broad, 1H), 5.06 (d, 1H), 3.9-3.78 (m, 2H), 3.71-3.62 (m, 2H), 3.31 (s, 3H), 3.22 (d, 1H), 2.90 (m, 1H), 2.82 (d, 1H), 2.55 (m, 1H), 2.48 (s broad, 1H), 2.41 (m, 1H), 2.35-2.20 (m, 3H), 1.93 (m, 1H), 1.25 (s, 9H). The reaction mixture was stirred at room temperature for 3 h was quenched by adding 2N aq. HCl solution EtOAc was added the solution was washed with 2N K2CO3 solution and with brine The organic phase was dried over Na2SO4 filtered evaporated

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: The title compound was prepared in analogous manner as described for example 1h) from (3R,4S,5S)-3-Amino-5-[4-nitro-3-fluoro-5-(2,2,2-trifluoro-ethoxy)-benzyl]-1,1-dioxo-hexahydro-1lambda*6*-thiopyran-4-ol hydrochloride salt (1.26 g, 2.78 mmol) and 3-tert-butyl benz-aldehyde (0.361 g, 2.26 mmol); ESIMS [M+H]+=563, UPLC RtD=1.576 min, 1H NMR (600 MHz, DMSO-d6): δ 7.35 (s, 1H), 7.27-7.21 (m, 2H), 7.15 (m, 2H), 7.10 (d, 1H), 5.32 (d, 1H), 5.01 (q, 2H), 3.81 (m, 1H), 3.63 (m, 1H), 3.38 (m, 1H), 3.20 (m, 1H), 3.10 (m, 1H), 3.05-2.98 (m, 2H), 2.80 (m, 2H), 2.63 (m, 1H), 2.41 (s, 1H), 2.14 (m, 1H), 1.25 (s, 9H). ESIMS [M+H]+=563, UPLC RtD=1.576 min, 1H NMR (600 MHz, DMSO-d6): δ 7.35 (s, 1H), 7.27-7.21 (m, 2H), 7.15 (m, 2H), 7.10 (d, 1H), 5.32 (d, 1H), 5.01 (q, 2H), 3.81 (m, 1H), 3.63 (m, 1H), 3.38 (m, 1H), 3.20 (m, 1H), 3.10 (m, 1H), 3.05-2.98 (m, 2H), 2.80 (m, 2H), 2.63 (m, 1H), 2.41 (s, 1H), 2.14 (m, 1H), 1.25 (s, 9H)

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of (3R*,4S*,5S*)-3-amino-5-(3-fluoro-4-nitro-benzyl)-1,1-dioxo-hexahydro-1lambda*6*-thiopyran-4-ol hydrochloride (0.14 g, 0.39 mmol) in MeOH-CH2Cl2 1:1 (3 mL) was added NaOAc (0.065 g, 0.78 mmol) and 3-tert-butyl-benzaldehyde (0.07 g, 0.43 mmol). The reaction mixture was stirred at 25° C. for 0.5 h before NaBH3CN (0.039 g, 0.59 mmol) was added followed by stirring for 16 h. The reaction mixture was acidified with 1N aq. HCl, stirred for 15 min, basified with K2CO3-solution and extracted with EtOAc. The combined organic layers were washed with brine, dried over MgSO4 and evaporated. The title compound was obtained after purification by flash-chromatography on silica gel (hexane-CH2Cl2-MeOH 20:20:1 to 1:20:5) as a light yellow foam: TLC (EtOAc) Rf=0.45; HPLC RtA=1.78 min; ESIMS [M+H]+=465; 1H NMR (400 MHz, CDCl3): δ 8.02 (t, 1H), 7.1-7.4 (m, 6H), 4.18 (s, 1H), 3.88 (d, 1H), 3.78 (d, 1H), 3.64 (m, 1H), 3.41 (ddd, 1H), 3.24 (ddd, 1H), 3.12 (dt, 1H), 3.00 (dd, 1H), 2.84, (m, 2H), 2.69 (m, 2H), 2.44 (m, 1H), 1.33 (s, 9H). was added stirred for 15 min extracted with EtOAc The combined organic layers were washed with brine dried over MgSO4 evaporated

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of (3R*,4S*,5S*)-3-amino-5-(3-fluoro-4-nitro-benzyl)-1,1-dioxo-hexahydro-1lambda*6*-thiopyran-4-ol hydrochloride (0.14 g, 0.39 mmol) in MeOH-CH2Cl2 1:1 (3 mL) was added NaOAc (0.065 g, 0.78 mmol) and 3-tert-butyl-benzaldehyde (0.07 g, 0.43 mmol). The reaction mixture was stirred at 25° C. for 0.5 h before NaBH3CN (0.039 g, 0.59 mmol) was added followed by stirring for 16 h. The reaction mixture was acidified with 1N aq. HCl, stirred for 15 min, basified with K2CO3-solution and extracted with EtOAc. The combined organic layers were washed with brine, dried over MgSO4 and evaporated. The title compound was obtained after purification by flash-chromatography on silica gel (hexane-CH2Cl2-MeOH 20:20:1 to 1:20:5) as a light yellow foam: TLC (EtOAc) Rf=0.45; HPLC RtA=1.78 min; ESIMS [M+H]+=465; 1H NMR (400 MHz, CDCl3): δ 8.02 (t, 1H), 7.1-7.4 (m, 6H), 4.18 (s, 1H), 3.88 (d, 1H), 3.78 (d, 1H), 3.64 (m, 1H), 3.41 (ddd, 1H), 3.24 (ddd, 1H), 3.12 (dt, 1H), 3.00 (dd, 1H), 2.84, (m, 2H), 2.69 (m, 2H), 2.44 (m, 1H), 1.33 (s, 9H). was added stirred for 15 min extracted with EtOAc The combined organic layers were washed with brine dried over MgSO4 evaporated

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: The title compound was prepared in an analogous manner as described for example 1h, starting from (1S,3R,4S,5S)-3-amino-5-[3-fluoro-4-nitro-5-((R)-2,2,2-trifluoro-1-methoxy-methyl-ethoxy)-benzyl]-1-oxo-tetrahydro-thiopyran-4-ol TFA salt (310 mg, 0.7 mmol) and 3-tert-butyl-benzaldehyde and was obtained after purification by flash-chromatography (hexane-(EtOAc-MeOH 9:1) gradient) as a light yellow foam: TLC (EtOAc-MeOH 9:1) Rf=0.38; HPLC RtH1=1.05 min; ESIMS [M+H]+=591; 1H NMR (600 MHz, CDCl3): δ 7.36 (s, 1H), 7.28 (s, 1H), 7.23 (m, 2H), 7.13 (d, 1H), 7.11 (d, 1H), 5.66 (m, 1H), 5.16 (d, 1H), 3.83-3.79 (m, 2H), 3.69 (dd, 1H), 3.63 (d, 1H), 3.55 (m, 1H), 3.30 (s, 3H), 3.14 (m, 2H), 3.00 (d, 1H), 2.55 (m, 1H), 2.5-2.4 (m, 3H), 1.95 (m, 1H), 1.25 (s, 9H). was obtained after purification by flash-chromatography (hexane-(EtOAc-MeOH 9:1) gradient) as a light yellow foam HPLC RtH1=1.05 min

反应条件: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of (3R,4S,5S)-3-amino-5-[3-fluoro-4-nitro-5-((R)-2,2,2-trifluoro-1-methoxy-methyl-ethoxy)-benzyl]-tetrahydro-thiopyran-4-ol hydrochloride (1.217 g, 2.52 mmol) in MeOH-CH2Cl2 1:2 (28 mL) was added NaOAc (0.517 g, 6.3 mmol), powdered molecular sieves (4A) and 3-tert-butyl-benzaldehyde (CAS registry 23039-28-3) (0.413 g, 2.55 mmol). The reaction mixture was stirred at 25° C. for 16 h, acetic acid (0.5 mL) was added followed by NaBH3CN (0.396 g, 6.3 mmol). The reaction mixture was stirred at room temperature for 3 h and was quenched by adding 2N aq. HCl solution. EtOAc was added and the solution was washed with 2N K2CO3 solution and with brine. The organic phase was dried over Na2SO4, filtered and evaporated. The title compound was obtained after purification by flash-chromatography on NH4OH deactivated silica gel (90 g, toluene-EtOAc 1:1) as a light yellow oil: TLC (toluene-ETA 85:15) Rf=0.52; HPLC RtA=2.178 min; ESIMS [M+H]+=575; 1H NMR (600 MHz, CDCl3): δ 7.33 (s, 1H), 7.28 (s, 1H), 7.26 (m, 2H), 7.18-7.08 (m, 2H), 5.7 (broad, 1H), 5.06 (d, 1H), 3.9-3.78 (m, 2H), 3.71-3.62 (m, 2H), 3.31 (s, 3H), 3.22 (d, 1H), 2.90 (m, 1H), 2.82 (d, 1H), 2.55 (m, 1H), 2.48 (s broad, 1H), 2.41 (m, 1H), 2.35-2.20 (m, 3H), 1.93 (m, 1H), 1.25 (s, 9H). The reaction mixture was stirred at room temperature for 3 h was quenched by adding 2N aq. HCl solution EtOAc was added the solution was washed with 2N K2CO3 solution and with brine The organic phase was dried over Na2SO4 filtered evaporated