Sodium Bicarbonate → (9-(2-Fluoro-3-(3-hydroxypropyl)benzyl)-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)(2-isopropylthiazol-4-yl)methanone

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Reaction Steps

3-(3-(tert-Butyldimethylsilyloxy)propyl)-2-fluorobenzaldehyde (example 88, step c) (0.15 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) (0.19 g) and acetic acid (0.03 mL) in N-methyl-2-pyrrolidinone (10 mL). The resulting mixture was stirred for 15 min then cooled in an ice bath. Sodium triacetoxyborohydride (0.16 g) was then added and the mixture stirred overnight. The reaction was poured into a mixture of saturated sodium hydrogen carbonate solution (20 mL) and water (100 mL). The aqueous was extracted with ethyl acetate (3×100 mL). The combined organics were washed with water (50 mL) and brine (100 mL), dried over sodium sulphate, filtered and evaporated. The residue was redissolved in THF (10 mL) and a solution of TBAF (1M in THF, 1.52 mL) was added. The resulting mixture was stirred for 2 h and the solvent evaporated. The residue was purified by column chromatography eluting with 4:1 isohexane:ethyl acetate+5% triethylamine to ethyl acetate+5% triethylamine gradient. The fractions containing product were combined and evaporated to give the subtitled compound as a clear oil. Yield 0.22 g.

Provenance & Evidence