反应详情

温度

40 °C

Add borane tetrahydrofuran complex (171 mL, 171 mmol) to a solution of tert-butyl 4-(4-fluorophenyl)-3,6-dihydro-2H-pyridine-1-carboxylate (54 g, 186 mmol) in THF (544 mL) under a nitrogen atmosphere. Stir overnight at 40° C., then add 2M sodium hydroxide (36.8 g, 70.8 mmol) and stir for 12 minutes at ambient temperature. Add hydrogen peroxide (31.1 mL, 357.8 mmol) while maintaining the internal temperature at 19-21° C. through the use of an ice-water bath. After addition is complete, remove the ice bath and stir at ambient temperature for 3 hours. Dilute the reaction mixture with water (250 mL) and extract twice with methyl tert-butyl ether (500 mL). Combine organic extracts, and sequentially wash with brine, sodium bisulfate then brine again. Dry the organics over magnesium sulphate; filter; collect the filtrate; and concentrate under vacuum. Purify the crude material via flash column chromatography using hexane/ethyl acetate (4:1, then 3:1) followed by DCM/EtOAc (1:1, then 0:100). Combine product fractions and dry under vacuum to give a white solid. Separate enantiomers using chromatography conditions “L” (see below), collecting the first eluting isomer to give the title compound (20.02 g, 36.4%) as a white solid. MS (m/z): 196 (M+1-Boc).

1. stirringstir for 12 minutes at ambient temperature
2. additionAfter addition
3. customremove the ice bath
4. stirringstir at ambient temperature for 3 hours
5. additionDilute the reaction mixture with water (250 mL)
6. extractionextract twice with methyl tert-butyl ether (500 mL)
7. washCombine organic extracts, and sequentially wash with brine, sodium bisulfate
8. dry with materialDry the organics over magnesium sulphate
9. filtrationfilter
10. customcollect the filtrate
11. concentrationand concentrate under vacuum
12. customPurify the crude material via flash column chromatography
13. customCombine product fractions and dry under vacuum
14. customto give a white solid
15. customcollecting the first eluting isomer