反应详情

A solution of 3-(2-(tert-butyldimethylsilyloxy)-1-fluoroethyl)benzaldehyde (example 39, step d) (0.329 g) in MeOH (4 mL) was treated with acetic acid (0.055 mL) followed by (2-isopropylthiazol-4-yl)(1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)methanone trifluoroacetate (example 22, step b) (0.408 g) and stirred at room temperature for 5 minutes. The solution was cooled in an ice-water bath, treated with sodium triacetoxyborohydride (0.309 g), stirred in ice-water for 135 minutes, then removed from the cooling bath and stirred at room temperature for a further 65 minutes. The solution was cooled back down in ice-water, treated with more sodium triacetoxyborohydride (0.310 g) and stirred in ice-water for 75 minutes. More sodium triacetoxyborohydride (0.312 g) was added and the mixture was stirred for 70 minutes. More sodium triacetoxyborohydride (0.619 g) was added and the mixture was stirred overnight, allowing the cooling bath to slowly expire. The next day, more sodium triacetoxyborohydride (0.307 g) was added and the mixture was stirred for 70 minutes. More acetic acid (0.055 mL) was added and the mixture was stirred for 80 minutes. The mixture was warmed to 40° C. and stirred at that temperature for 25 minutes, then it was concentrated onto flash silica in vacuo. The residue was purified by flash chromatography on silica eluted with 5% methanol in dichloromethane to afford the subtitled compound as a sticky white solid. Yield 0.344 g.

1. temperatureThe solution was cooled in an ice-water bath
2. customremoved from the cooling bath
3. stirringstirred at room temperature for a further 65 minutes
4. temperatureThe solution was cooled back down in ice-water
5. additiontreated with more sodium triacetoxyborohydride (0.310 g)
6. stirringstirred in ice-water for 75 minutes
7. additionMore sodium triacetoxyborohydride (0.312 g) was added
8. stirringthe mixture was stirred for 70 minutes
9. additionMore sodium triacetoxyborohydride (0.619 g) was added
10. stirringthe mixture was stirred overnight
11. additionThe next day, more sodium triacetoxyborohydride (0.307 g) was added
12. stirringthe mixture was stirred for 70 minutes
13. additionMore acetic acid (0.055 mL) was added
14. stirringthe mixture was stirred for 80 minutes
15. temperatureThe mixture was warmed to 40° C.
16. stirringstirred at that temperature for 25 minutes
17. concentrationit was concentrated onto flash silica in vacuo
18. customThe residue was purified by flash chromatography on silica
19. washeluted with 5% methanol in dichloromethane