Dimethyl Sulfoxide → 1-(2-Chloro-9,10-dihydro-9,10-methanoanthracen-9-ylmethyl)-4-(3-pyridyl)piperidin-4-ol

Temperature

-78 °C

To a cooled solution (-78° C.) of oxalyl chloride (3.06 mL, 35.1 mmol, 2 eq) in methylene chloride (100 mL) under nitrogen was added distilled dimethylsulfoxide (5.00 mL, 70.2 mmol, 4 eq). After 10 min 1-(2-chloro-9,10-dihydro-9,10-methanoanthracen-9-ylmethyl) piperidin-4-ol (described in example 11) (5.96 g, 17.5 mmol) was added as a methylene chloride solution (10 mL). The reaction was stirred at -78° C. for 30 min prior to the addition of triethylamine (19.6 mL, 140 mmol, 8 eq). The cooling bath was removed and the reaction warmed to room temperature over 1.5 h. The reaction was poured into 2.5N NaOH (100 mL) and the aqueous phase extracted with methylene chloride (3×100 mL). Combined organic extracts were dried over anhydrous magnesium sulfate, filtered, and reduced to an oil. The crude reaction mixture was purified by flash chromatography over silica gel (400 mL, eluent: 20% ethyl acetate in hexane) to yield 5.53 g (93%) of the title compound. TLC analysis (Rf 0.21, 20% ethyl acetate in hexane). 1H NMR (CDCl3, 250 MHz) 7.26 (m, 1H), 7.13 (m, 3H), 6.95 (m, 3H), 4.28 (s, 1H), 3.49 (s, 2H), 2.94 (t, J=6.1 Hz, 4H), 2.62 (s, 2H), 2.43 (t, J=6.0 Hz, 4H) MS (CI, CH4) m/z 338 (M+1,100), 340 (35), 366 (M+29,31).

1. customThe cooling bath was removed
2. temperaturethe reaction warmed to room temperature over 1.5 h
3. additionThe reaction was poured into 2.5N NaOH (100 mL)
4. extractionthe aqueous phase extracted with methylene chloride (3×100 mL)
5. dry with materialCombined organic extracts were dried over anhydrous magnesium sulfate
6. filtrationfiltered
7. customThe crude reaction mixture
8. customwas purified by flash chromatography over silica gel (400 mL, eluent: 20% ethyl acetate in hexane)

ORD record

ord-be364fe4248a46d5b62dfa8870f4e619

Source dataset

uspto-grants-1996_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05512575