Trifluoroacetic acid → HCID 10477811, compound

Participants

Reaction Steps

Part F. Preparation of 4-{[4-(5-butylthien-2-yl)piperidin-1-yl]sulfonyl}-N-(tetrahydro-2H-pyran-2-yloxy)tetrahydro-2H-pyran-4-carboxamide. A methylene chloride solution (8.0 mL) of the ester prepared in Part E (3.27 g, 6.93 mmol) was treated with trifluoroacetic acid (8.0 mL, 104 mmol) and stirred at ambient temperature. After 4 hr, the mixture was concentrated in vacuo to approximately 8.0 mL, then treated with diethyl ether (15 mL). The resulting mixture was concentrated in vacuo to approximately 4.0 mL, then treated with diethyl ether (15 mL). The resulting precipitate was filtered, washed with diethyl ether, and dried in vacuo. The resulting white solid (2.93 g) was dissolved in N,N-dimethylformamide (14.1 mL), treated with 1-(3-dimethylamino-propyl)-3-ethylcarbodiimide hydrochloride (2.03 g, 10.6 mmol) and N-hydroxybenzo-triazole hydrate (1.43 g, 10.6 mmol), and stirred at ambient temperature under N2. After 1 hr, the resulting suspension was treated with O-(tetrahydro-2H-pyran-2-yl)hydroxylamine (1.24 g, 10.6 mmol), followed by N-methylmorpholine (2.33 mL, 21.2 mmol). After 30 min, the mixture was diluted with ethyl acetate (100 mL) and partitioned with water (50 mL). The aqueous layer was separated and then extracted with ethyl acetate (25 mL). The organic layers were combined, washed with saturated NaHCO3 (25 mL), washed with 1:1 brine/water (25 mL), washed with brine (25 mL), dried over Na2SO4, filtered, and concentrated in vacuo. The resulting oil was purified on silica, eluting with 1:1 hexanes/ethyl acetate to produce the product in the form of a colorless glassy solid having an 11:4 mixture of desired product/impurity (3.52 g, 98.6% mass recovery). LC/MS m/z=537 [M+Na] for desired product

Provenance & Evidence