(1R,2S)-2-氨基-3-氟-1-(4-碘苯基)丙-1-醇

反应条件: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of 5-(4,4,5,5-Tetramethyl-[1,3,2]dioxaborolan-2-yl) -pyridine-2-carbonitrile (0.5 g, 2.17 mmol) in dimethoxyethane (10 mL) and water (3 mL) is added (1R,2S)-2-Amino-3-fluoro-1-(4-iodo-phenyl)-propan-1-ol (0.65 g, 2.20 mmol) and Cs2CO3 (2.15 g, 6.59 mmol), and degassed with nitrogen followed by addition of Pd(PPh3)4 (0.25 g, 0.21 mmol) and heated the reaction mixture to 90° C. for 1.5 hours. Solvent is evaporated in vacuo, to get crude material purified by column chromatography eluting in 2.5 to 3% methanol in CH2Cl2 to afford the title compound (0.3 g) as impure. 1H NMR (400 MHz, DMSO-d6) δ: 3.09-3.18 (m, 1H), 3.48 (s, 1H), 4.24-4.28 (m, 0.5H), 4.36-4.41 (m, 1H), 4.49-4.52 (m, 0.5H), 4.64 (d, J=6.16 Hz, 1H), 7.53 (d, J=8.16 Hz, 2H), 7.59 (d, J=8.24 Hz, 2H), 7.76 (d, J=8.2, 1H), 8.0 (dd, J1=8.16 Hz, J2=2.32 Hz, 1H), 8.93 (d, J=1.76 Hz, 1H). LC-MS (m/z): [M+H]=272.00. degassed with nitrogen Solvent is evaporated in vacuo to get crude material purified by column chromatography eluting in 2.5 to 3% methanol in CH2Cl2

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

实验步骤: Acetone (150 mL) is added to commercially available (1R,2S)-2-amino-3-fluoro-1-(4-iodophenyl)propan-1-ol (15.0 g, 50.8 mmol). After stirring overnight at room temperature the solvent is removed under reduced pressure to give the title compound (17.6 g): m/z (Cl) M+H 335. is removed under reduced pressure

反应条件: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of commercially available 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)picolinonitrile (0.5 g, 2.17 mmol) in degassed dimethoxyethane (10 mL) and water (3 mL) is added (1R,2S)-2-amino-3-fluoro-1-(4-iodophenyl)-propan-1-ol (0.65 g, 2.20 mmol) and Cs2CO3 (2.15 g, 6.6 mmol). Pd(PPh3)4 (0.25 g, 0.21 mmol) is added and the reaction mixture heated to 90° C. for 1.5 hours.

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

实验步骤: Commercially available (1R,2S)-2-amino-3-fluoro-1-(4-iodophenyl)propan-1-ol (6.0 g, 20.0 mmol) is dissolved in acetone (150 mL) and the mixture stirred at room temperature for 16 hours. The solvent is removed under reduced pressure to give the title compound (7.0 g). m/z (Cl) M+H 295. The solvent is removed under reduced pressure

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

实验步骤: To a solution of commercially available (1R,2S)-2-amino-3-fluoro-1-(4-iodophenyl)propan-1-ol (5.0 g, 20.0 mmol) in methanol (100 mL) is added triethylamine (9.56 mL, 67.8 mmol) and ethyldichloroacetate (6.22 mL, 50.8 mmol) and the mixture heated to reflux for 16 hours. After allowing to cool to room temperature, the solvent is removed under reduced pressure the resultant oil purified by column chromatography eluting from neat heptanes to 80% ethylacetate/heptanes to give the title compound (5.94 g). m/z (Cl) M+H 405. the mixture heated to reflux for 16 hours the solvent is removed under reduced pressure the resultant oil purified by column chromatography eluting from neat heptanes to 80% ethylacetate/heptanes

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

实验步骤: To a solution of commercially available (1R,2S)-2-amino-3-fluoro-1-(4-iodophenyl)propan-1-ol (5.0 g, 20.0 mmol) in methanol (100 mL) is added triethylamine (9.56 mL, 67.8 mmol) and ethyldichloroacetate (6.22 mL, 50.8 mmol) and the mixture heated to reflux for 16 hours. After allowing to cool to room temperature, the solvent is removed under reduced pressure the resultant oil purified by column chromatography eluting from neat heptanes to 80% ethylacetate/heptanes to give the title compound (5.94 g). m/z (Cl) M+H 405. the mixture heated to reflux for 16 hours the solvent is removed under reduced pressure the resultant oil purified by column chromatography eluting from neat heptanes to 80% ethylacetate/heptanes

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

实验步骤: To a solution of commercially available (1R,2S)-2-amino-3-fluoro-1-(4-iodophenyl)propan-1-ol (5.0 g, 20.0 mmol) in methanol (100 mL) is added triethylamine (9.56 mL, 67.8 mmol) and ethyldichloroacetate (6.22 mL, 50.8 mmol) and the mixture heated to reflux for 16 hours. After allowing to cool to room temperature, the solvent is removed under reduced pressure the resultant oil purified by column chromatography eluting from neat heptanes to 80% ethylacetate/heptanes to give the title compound (5.94 g). m/z (Cl) M+H 405. the mixture heated to reflux for 16 hours the solvent is removed under reduced pressure the resultant oil purified by column chromatography eluting from neat heptanes to 80% ethylacetate/heptanes

反应条件: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of 5-(4,4,5,5-Tetramethyl-[1,3,2]dioxaborolan-2-yl)-pyridine-2-carbonitrile (0.5 g, 2.17 mmol) in dimethoxyethane (10 mL) and water (3 mL) is added (1R,2S)-2-Amino-3-fluoro-1-(4-iodo-phenyl)-propan-1-ol (0.65 g, 2.20 mmol) and Cs2CO3 (2.15 g, 6.59 mmol), and degassed with nitrogen followed by addition of Pd(PPh3)4 (0.25 g, 0.21 mmol) and heated the reaction mixture to 90° C. for 1.5 hours. Solvent is evaporated in vacuo, to get crude material purified by column chromatography eluting in 2.5 to 3% methanol in CH2Cl2 to afford the title compound (0.3 g) as impure. 1H NMR (400 MHz, DMSO-d6) δ: 3.09-3.18 (m, 1H), 3.48 (s, 1H), 4.24-4.28 (m, 0.5H), 4.36-4.41 (m, 1H), 4.49-4.52 (m, 0.5H), 4.64 (d, J=6.16 Hz, 1H), 7.53 (d, J=8.16 Hz, 2H), 7.59 (d, J=8.24 Hz, 2H), 7.76 (d, J=8.2, 1H), 8.0 (dd, J1=8.16 Hz, J2=2.32 Hz, 1H), 8.93 (d, J=1.76 Hz, 1H). LC-MS (m/z): [M+H]=272.00. degassed with nitrogen Solvent is evaporated in vacuo to get crude material purified by column chromatography eluting in 2.5 to 3% methanol in CH2Cl2

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

实验步骤: Acetone (150 mL) is added to commercially available (1R,2S)-2-amino-3-fluoro-1-(4-iodophenyl)propan-1-ol (15.0 g, 50.8 mmol). After stirring overnight at room temperature the solvent is removed under reduced pressure to give the title compound (17.6 g): m/z (C1) M+H 335. is removed under reduced pressure

反应条件: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of commercially available 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)picolinonitrile (0.5 g, 2.17 mmol) in degassed dimethoxyethane (10 mL) and water (3 mL) is added (1R,2S)-2-amino-3-fluoro-1-(4-iodophenyl)-propan-1-ol (0.65 g, 2.20 mmol) and Cs2CO3 (2.15 g, 6.6 mmol). Pd(PPh3)4 (0.25 g, 0.21 mmol) is added and the reaction mixture heated to 90° C. for 1.5 hours. Solvent is evaporated in vacuo and the crude material purified by column chromatography on silica gel eluting in methanol/CHCl3 to afford the title compound (206 mg): 1NMR (400 MHz, CDCl3) δ: 3.09-3.18 (m, 1H), 3.48 (s, 1H), 4.24-4.28 (m, 0.5H), 4.36-4.41 (m, 1H), 4.49-4.52 (m, 0.5H), 4.64 (d, J=6.16 Hz, 1H), 7.53 (d, J=8.16 Hz, 2H), 7.59 (d, J=8.24 Hz, 2H), 7.76 (d, J=8.2, 1 H), 8.0 (dd, J1=8.16 Hz, J2=2.32 Hz, 1H), 8.93 (d, J=1.76 Hz, 1H). m/z (Cl) 272 [M+H]. Solvent is evaporated in vacuo the crude material purified by column chromatography on silica gel eluting in methanol/CHCl3

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

实验步骤: Using the same procedure as Step 1 of Example 4 and reacting ethyldifluoroacetate with commercially available (1R,2S)-2-amino-3-fluoro-1-(4-iodophenyl)propan-1-ol the title compound is obtained (18.3 g): m/z 373 (M+H)+.

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

实验步骤: Acetone (150 mL) is added to commercially available (1R,2S)-2-amino-3-fluoro-1-(4-iodophenyl)propan-1-ol (15.0 g, 50.8 mmol). After stirring overnight at room temperature the solvent is removed under reduced pressure to give the title compound (17.6 g): m/z (Cl) M+H 335. is removed under reduced pressure