Hydrochloric Acid → 3-Chloro-5-methoxybenzeneacetonitrile

Participants

Reaction Conditions

Reaction Steps

To a solution of 38b (13.3 g, 77 mmol, 1.0 equiv.) in 200 mL of dichloromethane cooled at −40° C. was added methanesulfonyl chloride (7.45 mL, 96 mmol, 1.25 equiv.), followed by dropwise addition of triethylamine (12.9 mL, 92 mmol, 1.2 equiv.). The mixture was stirred at −40° C. for 1 h. LiBr (20.0 g, 231 mmol, 3.0 equiv.) was added, followed by 400 mL of THF. The mixture was warmed to 0° C. After stirring at 0° C. for another 2 h, the mixture was poured into 200 mL of 1 M aqueous HCl. The mixture was evaporated in vacuo to remove organic solvents. The residue was extracted with 400 mL of ether. The ether layer was washed with 150 mL of saturated NaHCO3, 150 mL of brine, dried over Na2SO4, and evaporated in vacuo to give a light tan oil, which was dissolved in 100 mL of DMSO. NaCN (4.15 g, 85 mmol, 1.1 equiv.) was added to the solution. The mixture was stirred vigorously for 14 h. The mixture was poured into 300 mL of q water. The aqueous mixture was extracted with 200 mL of ether. The ether extracts were washed with 100 mL of saturated NaHCO3, 100 mL of brine, dried over Na2SO4, and evaporated in vacuo to give 9.8 g of a brown oil. 1H-NMR (DMSO-d6): δ 7.00 (m, 2H), 6.90 (m, 1H), 4.02 (s, 2H), 3.78 (s, 3H).

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