Tetrahydrofuran → HCID 117690725, compound

Temperature

27.5 °C

To a stirred solution of 3a (500 mg, 3.79 mmol) in dry THF (5 ml) was dropwise added a solution of n-butyl lithium in n-hexane (1.6M, 2.69 ml, 4.38 mmol) at −78° C. The resulting suspension was stirred at the same temperature for 0.5 h and treated dropwise with a solution of 1-benzylpiperidin-4-one (1.08 g, 5.68 mmol) in dry THF (10 ml). The reaction mixture was stirred −78° C. for 2 h, slowly warmed to 20-35° C. and continued stirring at 20-35° C. for 16 h. The progress of the reaction was monitored by TLC. The reaction mixture was quenched with NH4Cl solution (2 ml), diluted with water (20 ml) and extracted with ethyl acetate (2×50 ml). The combined organic layers were washed with brine (50 ml), followed by drying over anhydrous Na2SO4 and filtering. The filtrate was rotary evaporated to get residue which was purified by column chromatography using a mixture of 20% ethyl acetate/hexane as an eluent to get the desired compound as an off-white waxy solid (260 mg, 21%).

1. stirringThe reaction mixture was stirred −78° C. for 2 h
2. stirringcontinued stirring at 20-35° C. for 16 h
3. customThe reaction mixture was quenched with NH4Cl solution (2 ml)
4. additiondiluted with water (20 ml)
5. extractionextracted with ethyl acetate (2×50 ml)
6. washThe combined organic layers were washed with brine (50 ml)
7. dry with materialby drying over anhydrous Na2SO4
8. filtrationfiltering
9. customThe filtrate was rotary evaporated
10. customto get residue which
11. customwas purified by column chromatography
12. additiona mixture of 20% ethyl acetate/hexane as an eluent

ORD record

ord-9c66186342014d80bb7efdc1581feed3

Source dataset

uspto-grants-2015_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09062002B2