反应详情

2,4-Difluoro-3-(2-hydroxyethyl)benzaldehyde (example 45, step b) (0.35 g) was added to a solution of (2-isopropylthiazol-4-yl)(1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)methanone trifluoroacetate (example 22, step b) (0.67 g) and acetic acid (0.09 mL) in N-methyl-2-pyrrolidinone (1 mL). The resulting mixture was stirred for 1 h then quenched by portionwise addition of sodium triacetoxyborohydride (0.335 g) over 5 min. The resulting mixture was stirred overnight, diluted with acetonitrile (20 mL) and applied to a SCX cartridge (10 g Varian, pre-wetted with acetonitrile, (50 mL)). The cartridge was washed with acetonitrile (50 mL) and eluted with 10% ‘880’ aqueous ammonia in acetonitrile solution (50 mL). The eluent was evaporated, azeotroped with toluene and purified by silica gel chromatography eluting with 77.5:17.5:5 isohexane:ethyl acetate:triethylamine to 95:5 ethyl acetate:triethylamine gradient to give the subtitled compound as a yellow gum. Yield 0.74 g.

1. customthen quenched by portionwise addition of sodium triacetoxyborohydride (0.335 g) over 5 min
2. stirringThe resulting mixture was stirred overnight
3. additiondiluted with acetonitrile (20 mL)
4. washThe cartridge was washed with acetonitrile (50 mL)
5. washeluted with 10% ‘880’ aqueous ammonia in acetonitrile solution (50 mL)
6. customThe eluent was evaporated
7. customazeotroped with toluene
8. custompurified by silica gel chromatography
9. washeluting with 77.5:17.5:5 isohexane