Pyridine → Aniline

Participants

Reaction Steps

A solution of ethyl 4-hydroxy-2-methylcyclopentanecarboxylate (1.81 g, 10.5 mmol, prepared using P from Example #7, step G and NaBH4) and pyridine (1.28 mL, 15.8 mmol) in THF (52.5 mL) was cooled to about 0° C. Methanesulfonyl chloride (0.90 mL, 12 mmol) was added dropwise. The reaction mixture was stirred at ambient temperature for about 16 h then partitioned between water (50 mL) and DCM (30 mL). The layers were separated and the aqueous layer was extracted with DCM (2×30 mL). The combined organic layers were dried over anhydrous Na2SO4 and concd under reduced pressure to give a white solid. The resulting solid was mixed with aniline (78.0 g, 841 mmol) and heated at about 90° C. for about 16 h. The reaction mixture was concd under reduced pressure and purified by silica gel chromatography eluting with a gradient of 20-100% EtOAc in DCM to yield (1S,2R,4R)-ethyl 2-methyl-4-(phenylamino)cyclopentanecarboxylate and (1R,2S,4S)-ethyl 2-methyl-4-(phenylamino)cyclo-pentanecarboxylate with 29 mol % aniline as an excipient (2.73 g, 75%) as a dark oil: LC/MS (Table 1, Method b) Rt=2.67 min; MS m/z: 248 (M+H)+.

Provenance & Evidence