反应详情

温度

20 °C

A solution of (34-1-methyl-3,3-diphenyltetrahydro-3H-pyrrolo[1,2-c][1,3,2]oxazaborole (4.3 g, 16 mmol) in tetrahydrofuran (46 mL) was treated with 1.0 M borane-THF complex in tetrahydrofuran (19 mL, 19 mmol) and stirred at 20° C. for 15 min. The reaction mixture was cooled to −30° C. and treated with a solution of tert-butyl 3-(3-acetyl-5-chloro-6-cyano-2-methoxyphenyl)azetidine-1-carboxylate (5.7 g, 16 mmol) in tetrahydrofuran (49 mL) slowly. The flask containing the starting material ketone was rinsed with additional tetrahydrofuran (9 mL) and added to the reaction mixture. The temperature of the reaction was −20° C. after the addition was complete. The reaction mixture was warmed to −5° C. over a period of 30 min. The reaction mixture was quenched with water at 0° C., poured into saturated sodium bicarbonate solution, and extracted with ethyl acetate. The aqueous layer was separated and extracted with ethyl acetate. The combined organic layers were washed with water and brine, dried with magnesium sulfate, filtered, and concentrated to a crude dark oil. The crude material was purified by flash column chromatography using ethyl acetate in hexanes (0%-100%) to give the desired product (5.5 g, 97%) as a beige foam as a 97:3 mixture of enantiomers (Retention times=12.19 min and 13.18 min; Phenomenex Lux Cellulose C-2 column, 4.6×150 mm, 5 micron particle size, eluting with 8% ethanol in hexanes at 1 ml/min). 1H NMR (400 MHz, DMSO-d6) δ 7.62 (s, 1H), 5.48 (d, J=4.6 Hz, 1H), 5.00-4.90 (m, 1H), 4.43-4.31 (m, 1H), 4.30-4.10 (m, 4H), 3.66 (s, 3H), 1.38 (s, 9H), 1.29 (d, J=6.4 Hz, 3H). LCMS for C14H16ClN2O4 ([M-(t-Bu)+H]+H)+: m/z=311.1; Found: 311.1.

1. temperatureThe reaction mixture was cooled to −30° C.
2. washwas rinsed with additional tetrahydrofuran (9 mL)
3. additionadded to the reaction mixture
4. customwas −20° C.
5. additionafter the addition
6. temperatureThe reaction mixture was warmed to −5° C. over a period of 30 min
7. customThe reaction mixture was quenched with water at 0° C.
8. additionpoured into saturated sodium bicarbonate solution
9. extractionextracted with ethyl acetate
10. customThe aqueous layer was separated
11. extractionextracted with ethyl acetate
12. washThe combined organic layers were washed with water and brine
13. dry with materialdried with magnesium sulfate
14. filtrationfiltered
15. concentrationconcentrated to a crude dark oil
16. customThe crude material was purified by flash column chromatography