Hydrochloric Acid → 3-Chloro-5-methoxybenzeneacetonitrile

Temperature

-40 °C

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).

1. temperatureThe mixture was warmed to 0° C
2. stirringAfter stirring at 0° C. for another 2 h
3. customThe mixture was evaporated in vacuo
4. customto remove organic solvents
5. extractionThe residue was extracted with 400 mL of ether
6. washThe ether layer was washed with 150 mL of saturated NaHCO3, 150 mL of brine
7. dry with materialdried over Na2SO4
8. customevaporated in vacuo
9. customto give a light tan oil, which
10. stirringThe mixture was stirred vigorously for 14 h
11. extractionThe aqueous mixture was extracted with 200 mL of ether
12. washThe ether extracts were washed with 100 mL of saturated NaHCO3, 100 mL of brine
13. dry with materialdried over Na2SO4
14. customevaporated in vacuo

ORD record

ord-f699c726864b44eaab8497f62bb0ecb9

Source dataset

uspto-grants-2009_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07541383B2