[3-(1,1-difluoroethyl)phenyl]methanol

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Add a solution of [3-(1,1-Difluoro-ethyl)-phenyl]-methanol (3.47 mmol) in dichloromethane (10.5 mL) dropwise to a suspension of 3,3,3-triacetoxy-3-iodophthalide (3.64 mmol) in dichloromethane (10.5 mL) at room temperature. Stir for 30 minutes. Add diethyl ether (10 mL) and 5% aqueous sodium bicarbonate (10 mL) containing sodium thiosulfate (3 g). Mix well for 20 minutes. Separate the layers, and extract the aqueous with ethyl ether. Combine the organic layers, wash with brine, dry over sodium sulfate, filter, and evaporate to give a yellow solid. Purify over silica (40 g) eluting with 0 to 50% dichloromethane in hexanes. Evaporate until most solvent is removed being careful not to drive off the volatile product. Dry additionally by blowing a nitrogen stream over the product to give the title compound in 70% yield. 1HNMR (400.43 MHz, CDCl3): δ 10.03 (s, 1H), 8.00 (s, 1H), 7.92 (d, J=7.5 Hz, 1H), 7.75 (d, J=7.0 Hz, 1H), 7.59 (t, J=7.7 Hz, 1H), 1.98-1.89 (m, 3H). Mix well for 20 minutes Separate the layers extract the aqueous with ethyl ether wash with brine dry over sodium sulfate filter evaporate to give a yellow solid Purify over silica (40 g) eluting with 0 to 50% dichloromethane in hexanes Evaporate until most solvent is removed Dry additionally

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Add a solution of 3-(1,1-Difluoro-ethyl)-benzoic acid ethyl ester (3.57 mmol) in THF (5 mL) dropwise to a 1M solution of lithium aluminum hydride in THF (4.3 mL) at room temperature. Stir for 20 minutes then add ice followed by a mixture of concentrated sulfuric acid and ice (approximately 1:1 v:v). Extract with ethyl ether, dry the organic extracts over sodium sulfate, filter, and evaporate to give the title compound in 97% yield. GCMS MW 172 (M). 1H NMR (400.43 MHz, CDCl3): δ 7.49 (s, 1H), 7.41-7.39 (m, 3H), 4.70 (s, 2H), 1.94-1.85 (m, 3H). Extract with ethyl ether dry the organic extracts over sodium sulfate filter evaporate

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a suspension (100 ml) of lithium aluminum hydride (2.24 g, 54.4 mmol) in ether was added dropwise a solution of 3-(1,1-difluoroethyl)benzonitrile (5.48 g, 29.4 mmol) in ether (50 ml) under ice-cooling, and the mixture was stirred at room temperature for 4 hrs. After completion of the reaction, water (2.24 ml), 15% aqueous sodium hydroxide solution (2.24 ml) and water (6.72 ml) were successively added dropwise under ice-cooling. The obtained solid was filtered with celite and washed with ethyl acetate. The filtrate was concentrated, and the residue was purified by silica gel column chromatography (hexane:ethyl acetate=3:1, 1:1) to give 3-(1,1-difluoroethyl)benzyl alcohol (3.82 g, 75%) to give a colorless transparent oil. cooling were successively added dropwise under ice- cooling The obtained solid was filtered with celite washed with ethyl acetate The filtrate was concentrated the residue was purified by silica gel column chromatography (hexane:ethyl acetate=3:1, 1:1)