1-(Diphenylmethyl)azetidin-3-one → 1-Benzhydryl-3-methylazetidin-3-ol

Temperature

0 °C

To a solution of methylmagnesium bromide (263 mL, 790 mmol) in anhydrous THF (800 mL) was added a solution of 1-benzhydrylazetidin-3-one (75 g, 316 mmol) in THF (300 mL) rapidly with vigorous stirring at 0° C. The reaction mixture was stirred for 10 min, then allowed to warm to 25° C. and stirred for 2 h. The reaction mixture was quenched by the addition of saturated aqueous ammonium chloride (1 L), diluted with water (1 L) and extracted with EtOAc (3×1 L). The combined organic phase was washed with brine (0.5 L), dried over anhydrous Na2SO4 and filtered. The filtrate was evaporated in vacuo and the residue was purified by column chromatography on silica gel (eluting with 10-20% EtOAc in petroleum ether) to give 1-benzhydryl-3-methylazetidin-3-ol (65 g, 81%) as a white solid. 1H NMR (CDCl3, 400 MHz): δ 7.42 (m, 4H), 7.31 (m, 4H), 7.22 (m, 2H), 4.36 (s, 1H), 3.20 (m, 2H), 2.99 (m, 2H), 1.53 (s, 3H).

1. stirringThe reaction mixture was stirred for 10 min
2. temperatureto warm to 25° C.
3. stirringstirred for 2 h
4. customThe reaction mixture was quenched by the addition of saturated aqueous ammonium chloride (1 L)
5. additiondiluted with water (1 L)
6. extractionextracted with EtOAc (3×1 L)
7. washThe combined organic phase was washed with brine (0.5 L)
8. dry with materialdried over anhydrous Na2SO4
9. filtrationfiltered
10. customThe filtrate was evaporated in vacuo
11. customthe residue was purified by column chromatography on silica gel (eluting with 10-20% EtOAc in petroleum ether)

ORD record

ord-6d3d8a1e211d4fc8b3cad087e4e94b66

Source dataset

uspto-grants-2015_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09115151B2