Hydrochloric Acid → Trifluoroacetic acid

Participants

Reaction Conditions

Reaction Steps

A solution of methyl {(2S,3R)-1-[(1R)-4,4-dimethyl-1-(3,3,3-trifluoropropyl)pentyl]-2-[4-(trifluoromethyl)phenyl]piperidin-3-yl}acetate (3.9 g) in methanol (50 mL) was treated with 1M potassium hydroxide in methanol (25 mL, 25.0 mmol) was heated to 60° C. for 16 hours. The reaction was treated with 25 mL 1M HCl and partitioned between water and ethyl acetate. The organics were washed with brine, dried over sodium sulfate, filtered and evaporated in vacuo. The reaction was purified by reverse phase chromatography (35-100% acetonitrile/water) to give {(2S,3R)-1-[(1R)-4,4-dimethyl-1-(3,3,3-trifluoropropyl)pentyl]-2-[4-(trifluoromethyl)phenyl]piperidin-3-yl}acetic acid as its TFA salt. This salt was taken up in ethyl acetate and treated with 10 mL concentrated HCl and stirred vigorously for 24 hours. The solution was evaporated in vacuo to give exclusively the HCl salt. 1H NMR (600 MHz, CD3OD: δ 7.80 (bm, 4H), 4.65 (bm, 1H), 3.69 (bm, 1H), 3.22 (bm, 1H), 2.69 (bs, 2H), 2.24 (m, 1H), 2.12 (m, 4H), 2.04 (d, J=8.2 Hz, 1H), 2.01 (d, J=8.2 Hz, 1H), 1.91 (m, 3H), 1.66 (m, 1H), 1.51 (m, 1H), 1.13 (m, 1H), 0.92 (s, 9H), 0.74 (td, J=12.6, 3.8 Hz, 1H); LC/MS (EIMS, M+H)=482.1.

Provenance & Evidence