Methanol → HCID 67986524, compound

Temperature

80 °C

To a stirred solution of 0.500 mL (4.03 mmol) of 2-fluoroacetophenone and 0.50 g (2.68 mmol) of tert-butyl piperazine-1-carboxylate in 1.5 mL of anhydrous tetrahydrofuran under an atmosphere of nitrogen was added 2.50 mL (8.60 mmol) of titanium(IV) isopropoxide. The resulting mixture was heated to 80° C. for 12 h then cooled to 0° C. Next, 1.8 g (8.6 mmol) of solid sodium triacetoxyborohydride was added in one portion and the resulting solution was stirred with gradual warming to ambient temperature over 4 h. The reaction mixture was quenched with 1.0 mL (25 mmol) of methanol and then diluted with dichloromethane and a saturated aqueous sodium hydrogen carbonate solution. The mixture was filtered through a pad of Celite® and the layers separated. The aqueous phase was extracted with dichloromethane and the combined organic layers were washed with brine, dried over magnesium sulfate filtered and evaporated to dryness in vacuo. The crude residue was purified by silica gel chromatography eluting with a 0-100% ethyl acetate in hexanes gradient to afford the title compound as colorless oil (0.048 g, 58%). LC-MS: m/z (ES) 309.2 (MH)+

1. temperaturethen cooled to 0° C
2. temperaturewith gradual warming to ambient temperature over 4 h
3. filtrationThe mixture was filtered through a pad of Celite®
4. customthe layers separated
5. extractionThe aqueous phase was extracted with dichloromethane
6. washthe combined organic layers were washed with brine
7. dry with materialdried over magnesium sulfate
8. filtrationfiltered
9. customevaporated to dryness in vacuo
10. customThe crude residue was purified by silica gel chromatography
11. washeluting with a 0-100% ethyl acetate in hexanes gradient

ORD record

ord-64b92ed508004ab2b3641135c6036e37

Source dataset

uspto-grants-2013_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08354403B2