methyl 3,3,3-trifluoro-2-hydroxypropanoate

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of (±)-2-hydroxy-3,3,3-trifluoropropionic acid (7.8 g.), methanol (10 ml.) and concentrated sulphuric acid (0.5 ml.) is heated under reflux for 2 days. The cooled solution is poured into water (100 ml.), the mixture is saturated with sodium sulphate, and is extracted three times with ether. The extract is dried with sodium sulphate and evaporated. The residual oil (8.6 g.) is fractionally distilled to give (±)-methyl 2-hydroxy-3,3,3-trifluoropropionate b.p. 60°-64° C. at 12 mm. pressure, m.p. 50°-53° C. (3.9 g.). is heated under reflux for 2 days is extracted three times with ether The extract is dried with sodium sulphate evaporated The residual oil (8.6 g.) is fractionally distilled

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of (±)-2-hydroxy-3,3,3-trifluoropropionic acid (7.8 g.), methanol (10 ml.) and concentrated sulphuric acid (0.5 ml.) is heated under reflux for 2 days. The cooled solution is poured into water (100 ml.), the mixture is saturated with sodium sulphate, and is extracted three times with ether. The extract is dried with sodium sulphate and evaporated. The residual oil (8.6 g.) is fractionally distilled to give (±)-methyl 2-hydroxy-3,3,3-trifluoropropionate b.p. 60°-64° C. at 12 mm. pressure, m.p. 50°-53° C. (3.9 g.). is heated under reflux for 2 days is extracted three times with ether The extract is dried with sodium sulphate evaporated The residual oil (8.6 g.) is fractionally distilled

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a stirring solution of triphosgene (20 mg, 0.07 mmol) in CH2Cl2 (5.0 mL) was added methyl-3,3,3-trifluoro-DL-lactate (36 mg, 0.23 mmol) followed by N,N-diisopropylethylamine (120 μL, 0.69 mmol). After 2 h, N-methyl phenethylamine (31 mg, 0.23 mmol) was added as a solution in CH2Cl2 (2 mL) and stirred for another 2 h. The mixture was concentrated under reduced pressure and purified directly by SiO2 flash chromatography (25% EtOAc/hexanes) to provide the titled compound (47 mg, 64%): 1H NMR 500 MHz (CDCl3) δ 7.34-7.28 (m, 2H), 7.25-7.18 (m, 3H), 5.51-5.42 (m, 1H), 3.87 (s, 1.8H), 3.86 (s, 1.2H), 3.60-3.46 (m, 2H), 2.96-2.90 (m, 2.5H), 2.90-2.83 (m, 2.5H); HRMS m/z calc'd for [M+H]+ C14H16F3NO4: 320.1104. found 320.1109. The mixture was concentrated under reduced pressure purified directly by SiO2 flash chromatography (25% EtOAc/hexanes)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a stirring solution of triphosgene (20 mg, 0.07 mmol) in CH2Cl2 (5.0 mL) was added methyl-3,3,3-trifluoro-DL-lactate (36 mg, 0.23 mmol) followed by N,N-diisopropylethylamine (120 μL, 0.69 mmol). After 2 h, N-methyl phenethylamine (31 mg, 0.23 mmol) was added as a solution in CH2Cl2 (2 mL) and stirred for another 2 h. The mixture was concentrated under reduced pressure and purified directly by SiO2 flash chromatography (25% EtOAc/hexanes) to provide the titled compound (47 mg, 64%): 1H NMR 500 MHz (CDCl3) δ 7.34-7.28 (m, 2H), 7.25-7.18 (m, 3H), 5.51-5.42 (m, 1H), 3.87 (s, 1.8H), 3.86 (s, 1.2H), 3.60-3.46 (m, 2H), 2.96-2.90 (m, 2.5H), 2.90-2.83 (m, 2.5H); HRMS m/z calc'd for [M+H]+ C14H16F3NO4: 320.1104. found 320.1109. The mixture was concentrated under reduced pressure purified directly by SiO2 flash chromatography (25% EtOAc/hexanes)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a stirring solution of triphosgene (65 mg, 0.22 mmol) in CH2Cl2 (5.0 mL) was added methyl-3,3,3-trifluoro-DL-lactate (116 mg, 0.73 mmol) followed by N,N-diisopropylethylamine (0.38 mL, 2.19 mmol). After 2 h, 1-(bis(4-chlorophenyl)methyl)piperazine (160 mg, 0.50 mmol) was added as a solution in CH2Cl2 (2 mL) and stirred for another 2 h. The mixture was concentrated under reduced pressure and purified directly by SiO2 flash chromatography (25% EtOAc/hexanes) to provide the titled compound (156 mg, 62%): 1H NMR 500 MHz (CDCl3) δ 7.31 (d, J=8.47 Hz, 4H), 7.26 (d, J=8.41 Hz, 4H), 5.43 (q, J=7.03 Hz, 1H), 4.23 (s, 1H), 3.85 (s, 3H), 3.66-3.46 (m, 4H), 2.44-2.32 (m, 4H); HRMS m/z calc'd for [M+H]+ C22H21Cl2F3N2O4: 505.0903. found 505.0905. The mixture was concentrated under reduced pressure purified directly by SiO2 flash chromatography (25% EtOAc/hexanes)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a stirring solution of triphosgene (65 mg, 0.22 mmol) in CH2Cl2 (5.0 mL) was added methyl-3,3,3-trifluoro-DL-lactate (116 mg, 0.73 mmol) followed by N,N-diisopropylethylamine (0.38 mL, 2.19 mmol). After 2 h, 1-(bis(4-chlorophenyl)methyl)piperazine (160 mg, 0.50 mmol) was added as a solution in CH2Cl2 (2 mL) and stirred for another 2 h. The mixture was concentrated under reduced pressure and purified directly by SiO2 flash chromatography (25% EtOAc/hexanes) to provide the titled compound (156 mg, 62%): 1H NMR 500 MHz (CDCl3) δ 7.31 (d, J=8.47 Hz, 4H), 7.26 (d, J=8.41 Hz, 4H), 5.43 (q, J=7.03 Hz, 1H), 4.23 (s, 1H), 3.85 (s, 3H), 3.66-3.46 (m, 4H), 2.44-2.32 (m, 4H); HRMS m/z calc'd for [M+H]+ C22H21Cl2F3N2O4: 505.0903. found 505.0905. The mixture was concentrated under reduced pressure purified directly by SiO2 flash chromatography (25% EtOAc/hexanes)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: As described for example 112a, methyl-3,3,3-trifluoro-DL-lactate in butanol was reacted with hydrazine hydrate (1.2 equivalents) at rt for 16 h. The mixture was concentrated and the title compound was obtained as a light yellow oil (yield: 81%). MS: m/e=158.0 [M]+. The mixture was concentrated

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of (±)-2-hydroxy-3,3,3-trifluoropropionic acid (7.8 g.), methanol (10 ml.) and concentrated sulphuric acid (0.5 ml.) is heated under reflux for 2 days. The cooled solution is poured into water (100 ml.), the mixture is saturated with sodium sulphate, and is extracted three times with ether. The extract is dried with sodium sulphate and evaporated. The residual oil (8.6 g.) is fractionally distilled to give (±)-methyl 2-hydroxy-3,3,3-trifluoropropionate b.p. 60°-64° C. at 12 mm. pressure, m.p. 50°-53° C. (3.9 g.). is heated under reflux for 2 days is extracted three times with ether The extract is dried with sodium sulphate evaporated The residual oil (8.6 g.) is fractionally distilled