Hydrochloric Acid → HCID 18316935, compound

Participants

Reaction Steps

A split-neck jacketed reactor was equipped with a stirrer bar, thermometer, hypochlorite scrubber and pressure equalised dropping funnel. To this was charged 8-(2,2,2-trifluoroethyl)-8-azabicyclo[3.2.1]octan-3-one (3.04 g, 14.5 mmol) and diethyl ether (7 ml). The reaction mixture was agitated and cooled to 0+ C. (recirculating glycol), then around sodium cyanide (1 .07 g, 21.7 mmol) was added via a powder funnel. Hydrochloric acid (5M, 4.0 ml, 20.3 mmol) was added to the reaction mixture via a dropping funnel over 5 minutes and the reaction mixture was then stirred for 24 hours. The pH of the mixture was adjusted from 9 to 5.5 using hydrochloric acid (5M), and the organic layer was separated. The aqueous phase was extracted with diethyl ether (2×30 ml) and the combined organic extracts were washed with dilute hydrochloric acid (30 ml, pH 6). Sulphuric acid (98%, 2 drops) was added to the extracts before drying (MgSO4) and filtering. A further 2 drops of sulphuric acid were added then the ether extracts were concentrated in vacuo to give 3-cyano-3-hydroxy-8-(2,2,2-trifluoroethyl)-8-azabicyclo[3.2.1]octane ( 72:28 exo:endo cyano) as a pale yellow solution in diethyl ether. (Reaction conversion 83% by 1H NMR analysis.)

Provenance & Evidence