1-(3-fluorophenyl)propan-1-ol

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:5.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 18 L ethyl bromide were dissolved in 30 L of THF and added dropwise to a suspension of 6 kg of magnesium in 30 L of THF. The reaction solution was next stirred for two hours at 65° to 75° C. and then cooled to 0 to 10° C. 15 kg of 3-fluorobenzaldehyde in 60 L of THF were added while cooling with ice over a period of 6 hr and the reaction solution was stirred overnight at room temp. The reaction solution was quenched with saturated ammonium chloride solution at 0°-10° C. The reaction solution was stirred for one hour, organic layer separated and concentrated. The concentrate was extracted with 40 L of DCM and washed with 30 L of 5% HCl solution. The solvent was removed in vacuo. After drying, 20 kg of 1-(3-Fluoro -phenyl)-propan-1-ol were obtained as a brown oil and taken as such to the next step. while cooling with ice over a period of 6 hr the reaction solution was stirred overnight at room temp The reaction solution was quenched with saturated ammonium chloride solution at 0°-10° C The reaction solution was stirred for one hour organic layer separated concentrated The concentrate was extracted with 40 L of DCM washed with 30 L of 5% HCl solution The solvent was removed in vacuo After drying

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

実験手順: Anhydrous CH2Cl2 (10 mL) was cooled to −78° C., and anhydrous DMSO (0.546 g, 7.00 mmol) was added, followed, dropwise, by oxalyl chloride (0.380 g, 3.00 mmol). Once gas evolution ceased, compound 40 (0.308 g, 2 mmol) was added dropwise and the resulting milky solution was stirred for 15 min. Et3N (1.17 mL, 8.4 mmol) was added slowly and the mixture was stirred for 15 min at −78° C. and then warmed to room temperature and stirred for 1 h. The yellow mixture was diluted with H2O (30 mL) and the layers were separated. The aqueous layer was extracted with CH2Cl2 (2×15 mL), and the organic layers were washed with H2O and sat. aq. NaCl (15 mL each). The solution was dried over anhydrous sodium sulfate, concentrated, and the resulting residue was purified by flash column chromatography (SiO2), eluting with a gradient of hexanes to 10% EtOAc in hexanes to yield the title aldehyde as a colorless volatile oil (0.220 g, 72%). 1H-NMR (500 MHz; CDCl3): δ 9.82 (s, 1 H), 7.27-7.23 (m, 1 H), 6.97 (d, J=7.6 Hz, 1 H), 6.92-6.89 (m, 2 H), 2.96 (t, J=7.5 Hz, 2 H), 2.81-2.78 (m, 2 H). the mixture was stirred for 15 min at −78° C. stirred for 1 h the layers were separated The aqueous layer was extracted with CH2Cl2 (2×15 mL) the organic layers were washed with H2O and sat. aq. NaCl (15 mL each) The solution was dried over anhydrous sodium sulfate concentrated the resulting residue was purified by flash column chromatography (SiO2) eluting with a gradient of hexanes to 10% EtOAc in hexanes

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 3-Fluorophenylpropionic acid (39, 0.500 g, 2.97 mmol) was diluted in anhydrous THF (2 mL) under argon, and cooled to 0° C. Borane-THF (1 M, 4.16 mL, 4.16 mmol) was added dropwise, and the mixture was allowed to warm to room temperature and stirred for 18 h. The reaction was quenched by the addition of 1:1 THF/H2O (5 mL). When gas evolution ceased, solid K2CO3 was added until the mixture separated into two layers, which were separated. The aqueous layer was extracted with EtOAc (2×5 mL), and the combined organic layers were washed with H2O (15 mL) and sat. aq. NaCl (15 mL), dried over anhydrous sodium sulfate, and concentrated to yield the product as a clear oil (0.446 g, 97%) after drying in vacuo. 1H-NMR (500 MHz; CDCl3): δ 7.29-7.25 (m, 1 H), 7.00 (d, J=7.6 Hz, 1 H), 6.95-6.89 (m, 2 H), 3.71 (t, J=6.4 Hz, 2 H), 2.74 (t, J=7.7 Hz, 2 H), 1.95-1.89 (m, 2 H), 1.39 (s, 1 H). to warm to room temperature The reaction was quenched by the addition of 1:1 THF/H2O (5 mL) solid K2CO3 was added until the mixture separated into two layers, which were separated The aqueous layer was extracted with EtOAc (2×5 mL) the combined organic layers were washed with H2O (15 mL) and sat. aq. NaCl (15 mL) dried over anhydrous sodium sulfate concentrated