Trifluoroacetic acid → HCID 10477811, compound

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

1. concentrationthe mixture was concentrated in vacuo to approximately 8.0 mL
2. additiontreated with diethyl ether (15 mL)
3. concentrationThe resulting mixture was concentrated in vacuo to approximately 4.0 mL
4. additiontreated with diethyl ether (15 mL)
5. filtrationThe resulting precipitate was filtered
6. washwashed with diethyl ether
7. customdried in vacuo
8. dissolutionThe resulting white solid (2.93 g) was dissolved in N,N-dimethylformamide (14.1 mL)
9. stirringstirred at ambient temperature under N2
10. waitAfter 1 hr
11. waitAfter 30 min
12. custompartitioned with water (50 mL)
13. customThe aqueous layer was separated
14. extractionextracted with ethyl acetate (25 mL)
15. washwashed with saturated NaHCO3 (25 mL)
16. washwashed with 1:1 brine/water (25 mL)
17. washwashed with brine (25 mL)
18. dry with materialdried over Na2SO4
19. filtrationfiltered
20. concentrationconcentrated in vacuo
21. customThe resulting oil was purified on silica
22. washeluting with 1:1 hexanes/ethyl acetate
23. customto produce the product in the form of a colorless glassy solid

ORD record

ord-278d2a62e94d4f308dcab4286a834a62

Source dataset

uspto-grants-2006_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07119203B2