Acetic Acid → (9-(2-Fluoro-3-(1-hydroxy-2-methylpropan-2-yl)benzyl)-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)(2-isopropylthiazol-4-yl)methanone

Participants

Reaction Conditions

Reaction Steps

Sodium triacetoxyborohydride (0.502 g) was added to a stirred solution at 0° C. of (2-isopropylthiazol-4-yl)(1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)methanone trifluoroacetate (example 22, step b) (0.668 g) and 3-(1-(tert-butyldimethylsilyloxy)-2-methylpropan-2-yl)-2-fluorobenzaldehyde (example 90, step f) (0.49 g) and acetic acid (0.090 mL) in NMP (20 mL). The reaction mixture was then stirred at 20° C. for 18 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 tetrabutylammonium fluoride (1M in THF, 3.16 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, elution gradient 0 to 1% methanol in dichloromethane with 1% triethylamine. Pure fractions were evaporated to dryness to afford the subtitled compound. Yield 0.63 g.

Provenance & Evidence