Acetic Acid → (5-Ethylthiophen-3-yl)(9-(2-fluoro-5-(2-hydroxyethyl)benzyl)-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)methanone

温度

20 °C

Sodium triacetoxyborohydride (0.225 g) was added to a stirred solution at 0° C. of (5-ethylthiophen-3-yl)(1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)methanone trifluoroacetate (example 99, step a) (0.289 g) and 5-(2-(tert-butyldimethylsilyloxy)ethyl)-2-fluorobenzaldehyde (example 100, step b) (0.2 g) and acetic acid (0.041 ml) in NMP (20 mL). The reaction mixture was then stirred at 20° C. for 18 hours. Further sodium triacetoxyborohydride (0.150 g) was added and stirring continued for 4 hours. The mixture was partitioned between ethyl acetate and saturated sodium bicarbonate solution, the organic layer was washed twice with brine, dried over sodium sulphate, filtered and the solvent evaporated under reduced pressure. The resultant gum was dissolved in THF (20 mL) and treated with TBAF (1M in THF, 1.4 ml). The solution was allowed to stand at 20° C. for 8 hours. The solvent was evaporated under reduced pressure and the crude product was purified by flash silica chromatography using 2% methanol in dichloromethane with 1% triethylamine as solvent. Pure fractions were evaporated to dryness to afford the subtitled compound. Yield 0.18 g.

1. stirringstirring
2. waitcontinued for 4 hours
3. customThe mixture was partitioned between ethyl acetate and saturated sodium bicarbonate solution
4. washthe organic layer was washed twice with brine
5. dry with materialdried over sodium sulphate
6. filtrationfiltered
7. customthe solvent evaporated under reduced pressure
8. dissolutionThe resultant gum was dissolved in THF (20 mL)
9. additiontreated with TBAF (1M in THF, 1.4 ml)
10. waitto stand at 20° C. for 8 hours
11. customThe solvent was evaporated under reduced pressure
12. customthe crude product was purified by flash silica chromatography
13. customPure fractions were evaporated to dryness

ORDレコード

ord-1ef087eeafea4deea1dcfd47cb2de627

出典データセット

uspto-grants-2012_04

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08148373B2