Phenylphosphonic dichloride → (S)-1-(2-thiopheneacetyl)-3-piperidinonitrile

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Reaction Steps

(S)-1-(2-thiopheneacetyl)-3-piperidinecarboxaldehyde (117.4 mg. 0.50 mmol) was dissolved in dichloromethane (2.5 ml). Anhydrous methanol (80 l), dry pyridine (100 g), and hydroxylamine hydrochloride (38.2 mg; 0.55 mmol) were added and the mixture was allowed to stir at ambient temperature for 1 hour. The mixture was then evaporated under reduced pressure at ambient temperature. The residue was suspended in fresh dichloromethane (3 ml). Dry pyridine (80 μl) was added to this mixture, followed by dropwise addition of commercially available phenylphosphonic dichloride (140 μl; 1.0 mmol). After addition was complete, the mixture was allowed to stir at ambient temperature for 22 hours. Saturated sodium bicarbonate solution was then added. The mixture was diluted with dichloromethane and washed with fresh saturated sodium bicarbonate solution. The dichloromethane was then washed with saturated sodium chloride solution, dried with anhydrous potassium carbonate, and evaporated under reduced pressure at ambient temperature. The crude product was purified by chromatography on silica eluting with 50% ethyl acetate/50% hexane, giving (S)-1-(2-thiopheneacetyl)-3-piperidinonitrile (71.4 mg) as a pale yellow oil. MS m/z (positive ion) 235 (MH+; 100).

Provenance & Evidence