甲基(S)-环氧乙烷羧酸

反应条件: temp:85.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 3-((tert-Butyldiphenylsilyloxy)methyl)azetidine (Intermediate BG3) (7.461 g, 22.92 mmol) and (S)-methyl oxirane-2-carboxylate (2.340 g, 22.92 mmol) were dissolved in acetonitrile (50 mL) and heated to 85° C. for 90 minutes. The resulting mixture was cooled and evaporated to dryness. The crude product was purified by flash silica chromatography, elution gradient 0 to 5% MeOH in DCM to afford the product (9.6 g, 56%). The resulting mixture was cooled evaporated to dryness The crude product was purified by flash silica chromatography, elution gradient 0 to 5% MeOH in DCM

反应条件: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: (S)-Methyl oxirane-2-carboxylate (1475 mg, 14.45 mmol) in acetonitrile (2 mL)was added to azetidine (825 mg, 14.45 mmol) in acetonitrile (8 mL). The reaction was heated to 100° C. for 60 minutes in the microwave reactor and cooled to room temperature. The mixture was evaporated to afford the crude product (2.3 g) which was used without further purification. cooled to room temperature The mixture was evaporated

反应条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Magnesium trifluoromethanesulfonate (1.779 g, 5.52 mmol) was added in one portion to (S)-2-(tert-butyldimethylsilyloxy)propan-1-ol (Intermediate AS4) (4.2 g, 22.06 mmol) and (S)-methyl oxirane-2-carboxylate (2.252 g, 22.06 mmol) in EtOAc (25 mL). The resulting suspension was stirred at 80° C. for 24 hours. A further 1.5 g of the oxirane was added and the reaction stirred for 4 days. The reaction mixture was diluted with EtOAc, filtered through celite and evaporated to dryness. The crude product was purified by flash silica chromatography, elution gradient 0 to 30% EtOAc in isohexane to afford the product (2.70 g, 41.8%). 1H NMR (400 MHz, CDCl3) δ 0.00 (6H, d), 0.82 (9H, s), 1.06 (3H, d), 3.04 (1H, d), 3.25-3.39 (2H, m), 3.65-3.78 (5H, m), 3.83-3.92 (1H, m), 4.19-4.27 (1H, m) the reaction stirred for 4 days filtered through celite evaporated to dryness The crude product was purified by flash silica chromatography, elution gradient 0 to 30% EtOAc in isohexane

反应条件: temp:10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Magnesium trifluoromethanesulfonate (0.974 g, 3.02 mmol) was added in one portion to (S)-methyl oxirane-2-carboxylate (1.234 g, 12.08 mmol) and (S)-1-(tert-butyldimethylsilyloxy)propan-2-ol (CAS no. 113534-13-7) (2.30 g, 12.08 mmol) in EtOAc (5 mL) cooled to 10° C. The resulting suspension was stirred at 10° C. for 10 minutes and then warmed to 45° C. and stirred for 2 days. The crude product was purified by flash silica chromatography, eluting with 0 to 30% EtOAc in isohexane to afford the product (1.336 g, 37.8%). 1H NMR (400 MHz, DMSO) δ0.00 (s, 6H), 0.83 (s, 9H), 0.98 (d, 3H), 3.34-3.53 (m, 3H), 3.55-3.64 (m, 5H), 4.11 (q, 1H), 5.39 (d, 1H) warmed to 45° C. stirred for 2 days The crude product was purified by flash silica chromatography eluting with 0 to 30% EtOAc in isohexane

反应条件: temp:10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Magnesium trifluoromethanesulfonate (1.165 g, 3.61 mmol) was added in one portion to (S)-methyl oxirane-2-carboxylate (1.475 g, 14.45 mmol) and (R)-1-(tert-butyldimethylsilyloxy)propan-2-ol (CAS no. 136918-07-5) (2.75 g, 14.45 mmol) cooled to 10° C. The resulting suspension was stirred at 10° C. for 10 minutes and then warmed to 45° C. and stirred for 2 days. The crude product was purified by flash silica chromatography, eluting with 0 to 30% EtOAc in isohexane to afford the product (1.680 g, 39.8%). 1H NMR (400 MHz, DMSO) δ0.00 (s, 6H), 0.83 (s, 9H), 0.98 (d, 3H), 3.35-3.45 (m, 2H), 3.47-3.65 (m, 3H), 3.66 (s, 3H), 4.09-4.15 (m, 1H), 5.37 (d, 1H). warmed to 45° C. stirred for 2 days The crude product was purified by flash silica chromatography eluting with 0 to 30% EtOAc in isohexane

反应条件: temp:10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Magnesium trifluoromethanesulfonate (3.95 g, 12.24 mmol) was added in one portion to (S)-methyl oxirane-2-carboxylate (5 g, 48.98 mmol) and 2-(tert-butyldiphenylsilyloxy)ethanol (14.72 g, 48.98 mmol) at 10° C. The resulting suspension was stirred at 10° C. for 10 minutes and then warmed to 45° C. and stirred for 3 days. The crude product was purified by flash silica chromatography, eluting with 0 to 30% ethyl acetate in isohexane to afford the product (8.50 g, 43.1%). 1H NMR (400 MHz, CDCl3) δ 1.05 (9H, s), 3.10 (1H, d), 3.62 (2H, t), 3.74-3.87 (7H, m), 4.26-4.34 (1H, m), 7.35-7.46 (6H, m), 7.63-7.71 (4H, m); m/z (ESI+) (M+Na)+=425.37; HPLC tR=3.15 min. warmed to 45° C. stirred for 3 days The crude product was purified by flash silica chromatography eluting with 0 to 30% ethyl acetate in isohexane

反应条件: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Magnesium perchlorate (2.73 g, 12.24 mmol) was added in one portion to (S)-methyl oxirane-2-carboxylate (CAS no. 118712-39-3) (5 g, 48.98 mmol) and (R)-1-methoxypropan-2-ol (CAS no. 4984-22-9) (4.41 g, 48.98 mmol) at room temperature. The resulting suspension was stirred at 50° C. for 16 hours. The reaction mixture was diluted with ethyl acetate (50 mL) and washed with water (20 mL), dried (MgSO4) and evaporated. This was not isolated and used crude in next step. at room temperature washed with water (20 mL) dried (MgSO4) evaporated This was not isolated

反应条件: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Magnesium perchlorate (2.79 g, 12.49 mmol) was added in one portion to (S)-methyl oxirane-2-carboxylate (CAS no. 118712-39-3) (5.1 g, 49.96 mmol) and (S)-1-methoxypropan-2-ol (CAS no. 26550-55-0) (4.50 g, 49.96 mmol) at ambient temperature. The resulting suspension was stirred at 50° C. for 16 hours. The reaction mixture was diluted with DMF (50 mL) before adding 1H-imidazole (6.80 g, 99.92 mmol) and tert-butylchlorodimethylsilane (9.04 g, 59.95 mmol). The resulting solution was stirred at 40° C. for 5 hours. The reaction mixture was evaporated to dryness and re-dissolved in ethyl acetate (125 mL), and washed sequentially with water (50 mL) and saturated brine (25 mL). The organic layer was dried (MgSO4) and evaporated. The crude product was purified by flash silica chromatography, eluting with 0 to 50% ethyl acetate in isohexane to afford the product (4.52 g, 30%). 1H NMR (400 MHz, DMSO) δ 0.00 (d, 6H), 0.82 (s, 9H), 0.98 (d, 3H), 3.13-3.28 (m, 5H), 3.50-3.64 (m, 6H), 4.26-4.32 (m, 1H); m/z (ESI+) (M+H)+=307.19; HPLC tR=10.82 min. at ambient temperature The resulting solution was stirred at 40° C. for 5 hours The reaction mixture was evaporated to dryness re-dissolved in ethyl acetate (125 mL) washed sequentially with water (50 mL) and saturated brine (25 mL) The organic layer was dried (MgSO4) evaporated The crude product was purified by flash silica chromatography eluting with 0 to 50% ethyl acetate in isohexane

反应条件: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Magnesium perchlorate (2.79 g, 12.49 mmol) was added in one portion to (S)-methyl oxirane-2-carboxylate (CAS no. 118712-39-3) (5.1 g, 49.96 mmol) and (S)-1-methoxypropan-2-ol (CAS no. 26550-55-0) (4.50 g, 49.96 mmol) at ambient temperature. The resulting suspension was stirred at 50° C. for 16 hours. The reaction mixture was diluted with DMF (50 mL) before adding 1H-imidazole (6.80 g, 99.92 mmol) and tert-butylchlorodimethylsilane (9.04 g, 59.95 mmol). The resulting solution was stirred at 40° C. for 5 hours. The reaction mixture was evaporated to dryness and re-dissolved in ethyl acetate (125 mL), and washed sequentially with water (50 mL) and saturated brine (25 mL). The organic layer was dried (MgSO4) and evaporated. The crude product was purified by flash silica chromatography, eluting with 0 to 50% ethyl acetate in isohexane to afford the product (4.52 g, 30%). 1H NMR (400 MHz, DMSO) δ 0.00 (d, 6H), 0.82 (s, 9H), 0.98 (d, 3H), 3.13-3.28 (m, 5H), 3.50-3.64 (m, 6H), 4.26-4.32 (m, 1H); m/z (ESI+) (M+H)+=307.19; HPLC tR=10.82 min. at ambient temperature The resulting solution was stirred at 40° C. for 5 hours The reaction mixture was evaporated to dryness re-dissolved in ethyl acetate (125 mL) washed sequentially with water (50 mL) and saturated brine (25 mL) The organic layer was dried (MgSO4) evaporated The crude product was purified by flash silica chromatography eluting with 0 to 50% ethyl acetate in isohexane

反应条件: temp:10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Magnesium trifluoromethanesulphonate (11.85 g, 36.73 mmol) was added in one portion to (S)-methyl oxirane-2-carboxylate (15.0 g, 146.93 mmol) and ethanol (10.29 ml, 176.32 mmol) cooled to 10° C. The resulting suspension was stirred at 10° C. for 20 minutes, allowed to warm to ambient temperature and then warmed to 50° C. for 30 hours. The mixture was allowed to cool and diluted with 9:1 DCM:ether (75 mL), filtered through Celite and washed through with 9:1 DCM:ether (3×50 mL) and evaporated. The residue was purified by flash silica chromatography, elution gradient 10 to 50% Et2O in DCM to give methyl (2S)-3-ethoxy-2-hydroxypropanoate (11.6 g, 53%). 1H NMR (400 MHz, CDCl3) δ 1.19 (3H, t), 3.00 (1H, d), 3.47-3.58 (2H, m), 3.72 (2H, d), 3.81 (3H, s), 4.23-4.34 (1H, m). to warm to ambient temperature warmed to 50° C. for 30 hours to cool ether (75 mL), filtered through Celite washed through with 9:1 DCM ether (3×50 mL) and evaporated The residue was purified by flash silica chromatography, elution gradient 10 to 50% Et2O in DCM

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

实验步骤: (S)-Methyl oxirane-2-carboxylate (2.04 g, 19.98 mmol), magnesium trifluoromethanesulfonate (1.611 g, 5.00 mmol) and propan-2-ol (1.84 mL, 24.0 mmol) in ethyl acetate (10 mL) were heated at reflux for 90 hours. The mixture was diluted with EtOAc (20 mL), filtered and evaporated. The residue was purified by flash silica chromatography, elution gradient 20 to 50% EtOAc in isohexane to afford (S)-methyl 2-hydroxy-3-isopropoxypropanoate (2.45 g, 76%). 1H NMR (400 MHz, CDCl3) δ 1.13 (3H, d), 1.16 (3H, d), 3.00 (1H, d), 3.58-3.64 (1H, m), 3.68-3.74 (2H, m), 3.69-3.73 (1H, m), 3.80 (3H, s), 4.28-4.31 (1H, m) at reflux for 90 hours filtered evaporated The residue was purified by flash silica chromatography, elution gradient 20 to 50% EtOAc in isohexane

反应条件: temp:-30.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 72 ml (0.122 mol, 2.5 eq) of tert-butyllithium (1.7M/pentane) are added slowly using a needle to a suspension of 35 g (0.148 mol, 3 eq) of 1,4-dibromobenzene in 100 ml of tert-butyl methyl ether at −30° C. The mixture is stirred at −30° C. for 10 min and then 5.3 g (0.059 mol) of copper(I) cyanide are introduced into the above solution. The reaction mixture is stirred at −30° C. for 20 min. A solution of 5 g (0.049 mol) of methyl (S)-glycidate in 10 ml of tert-butyl methyl ether is added while keeping the temperature below −20° C. The mixture is stirred at −30° C. for 20 min and then the reaction is halted by the addition of a saturated ammonium chloride solution. The mixture is extracted with 3×300 ml of ethyl acetate. The organic phases are combined and dried over sodium sulfate. The solvents are evaporated and then the residue is chromatographed on silica gel (heptane 100% up to heptane/ethyl acetate 60/40). 7.2 g of methyl (S)-3-(4-bromophenyl)-2-hydroxypropionate are obtained in the form of a solid. Yield=56%. The reaction mixture is stirred at −30° C. for 20 min the temperature below −20° C The mixture is stirred at −30° C. for 20 min The mixture is extracted with 3×300 ml of ethyl acetate dried over sodium sulfate The solvents are evaporated the residue is chromatographed on silica gel (heptane 100% up to heptane/ethyl acetate 60/40)