5-chloro-4-(2-hydroxyethyl)-2-methoxybenzonitrile

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

Procedure: A solution of 2-(2-chloro-4-cyano-5-methoxyphenyl)ethanol (205 mg, 0.969 mmol) DIPEA (0.846 mL, 4.84 mmol) and pyridine (0.0780 mL, 0.969 mmol) in DCM (3 mL) was treated dropwise with mesyl chloride (0.110 mL, 1.42 mmol). The reaction was stirred for 2 hours and was then diluted with DCM and washed twice with aq. citric acid, then washed with brine, and dried over sodium sulfate. Purification of the residue by flash chromatography (20-50% ethyl acetate/hexanes) afforded the title intermediate. 1H-NMR (500 MHz, CDCl3) δ ppm 2.99 (s, 3H), 3.24 (t, J=6.6 Hz, 2H), 3.95 (s, 3H), 4.49 (t, J=6.6 Hz, 2H), 6.962 (s, 1H), 7.563 (s, 1H). washed twice with aq. citric acid washed with brine dried over sodium sulfate Purification of the residue by flash chromatography (20-50% ethyl acetate/hexanes)

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

Procedure: To a solution of methyl (2-chloro-4-cyano-5-methoxyphenyl)acetate (200 mg, 0.835 mmol) in THF (5 mL) was added 2M lithium borohydride (0.835 mL, 1.67 mmol) and the reaction was stirred at RT for 16 hours. The reaction was diluted with ether and quenched into water containing 2N HCl. The mixture was extracted twice with ethyl acetate and the organic layers were washed with brine, dried over sodium sulfate and concentrated in vacuo. The product mixture was separated by MPLC (40+S; 20-60% ethyl acetate/hexanes) to afford the title product. 1H-NMR (400 MHz, CDCl3) δ ppm 3.04 (t, J=6.4 Hz, 2H), 3.93 (t, J=6.4 Hz, 2H), 3.93 (s, 3H), 6.927 (s, 1H), 7.536 (s, 1H). quenched into water containing 2N HCl The mixture was extracted twice with ethyl acetate the organic layers were washed with brine dried over sodium sulfate concentrated in vacuo The product mixture was separated by MPLC (40+S; 20-60% ethyl acetate/hexanes)

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

Procedure: A solution of 2-(2-chloro-4-cyano-5-methoxyphenyl)ethanol (205 mg, 0.969 mmol) DIPEA (0.846 mL, 4.84 mmol) and pyridine (0.0780 mL, 0.969 mmol) in DCM (3 mL) was treated dropwise with mesyl chloride (0.110 mL, 1.42 mmol). The reaction was stirred for 2 hours and was then diluted with DCM and washed twice with aq. citric acid, then washed with brine, and dried over sodium sulfate. Purification of the residue by flash chromatography (20-50% ethyl acetate/hexanes) afforded the title intermediate. 1H-NMR (500 MHz, CDCl3) δ ppm 2.99 (s, 3H), 3.24 (t, J=6.6 Hz, 2H), 3.95 (s, 3H), 4.49 (t, J=6.6 Hz, 2H), 6.962 (s, 1H), 7.563 (s, 1H). washed twice with aq. citric acid washed with brine dried over sodium sulfate Purification of the residue by flash chromatography (20-50% ethyl acetate/hexanes)

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

Procedure: To a solution of methyl(2-chloro-4-cyano-5-methoxyphenyl)acetate (200 mg, 0.835 mmol) in THF (5 mL) was added 2M lithium borohydride (0.835 mL, 1.67 mmol) and the reaction was stirred at RT for 16 hours. The reaction was diluted with ether and quenched into water containing 2N HCl. The mixture was extracted twice with ethyl acetate and the organic layers were washed with brine, dried over sodium sulfate and concentrated in vacuo. The product mixture was separated by MPLC (40+S; 20-60% ethyl acetate/hexanes) to afford the title product. 1H-NMR (400 MHz, CDCl3) δ ppm 3.04 (t, J=6.4 Hz, 2H), 3.93 (t, J=6.4 Hz, 2H), 3.93 (s, 3H), 6.927 (s, 1H), 7.536 (s, 1H). quenched into water containing 2N HCl The mixture was extracted twice with ethyl acetate the organic layers were washed with brine dried over sodium sulfate concentrated in vacuo The product mixture was separated by MPLC (40+S; 20-60% ethyl acetate/hexanes)