Sodium triacetoxyborohydride → (9-(2-(2,3-Difluoro-4-(2-hydroxyethyl)phenoxy)ethyl)-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)(2-isopropylthiazol-4-yl)methanone

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Reaction Steps

(2-Isopropylthiazol-4-yl)(1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)methanone trifluoroacetate (example 22, step b) (0.5 g) was added to a solution of 2-(2,3-difluoro-4-(2-hydroxyethyl)phenoxy)acetaldehyde (example 77, step d) (0.31 g) in N-methyl-2-pyrrolidinone (10 mL) and acetic acid (0.07 mL). The resulting mixture was stirred for 30 min then cooled in an ice bath. Sodium triacetoxyborohydride (0.38 g) was then added and the reaction was allowed to warm to RT and stirred overnight. The reaction mixture was partitioned between ethyl acetate (100 mL) and water (100 mL). The aqueous phase was basified with saturated sodium hydrogen carbonate solution and the layers separated. The aqueous phase was extracted with ethyl acetate (2×100 mL). The combined organic solutions were washed with water (100 mL) and brine (100 mL), dried over sodium sulphate, filtered and evaporated. The residue was purified by silica gel chromatography, eluting with 47.5:47.5:5 isohexane:ethylacetate:triethylamine to 5% triethylamine in ethyl acetate. The fractions containing product were combined and evaporated to give the subtitled compound as a clear gum. Yield 0.41 g.

Provenance & Evidence