Sodium Bicarbonate → (9-((5-(2-(Tert-butyldimethylsilyloxy)ethyl)thiophen-3-yl)methyl)-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)(2-isopropylthiazol-4-yl)methanone

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Reaction Steps

5-(2-(tert-butyldimethylsilyloxy)ethyl)thiophene-3-carbaldehyde (0.6 g) (example 278, step c) was added to (2-isopropylthiazol-4-yl)(1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)methanone (0.94 g) (example 22, step b) in a mixture of N-methyl-2-pyrrolidinone (5 mL) and acetic acid (0.13 mL) and stirred for 30 min. Sodium triacetoxyborohydride (0.71 g) was then added and the mixture stirred overnight. The reaction was poured into water (100 mL), the pH was adjusted to 8 using saturated sodium bicarbonate solution and the resulting aqueous solution extracted with ethyl acetate (3×100 mL). The combined organic solutions were washed with water (3×100 mL), brine (100 mL), dried over sodium sulphate, filtered and evaporated. The residue was purified by silica gel chromatography eluting with 77.5:17.5:5 i-hexane:ethyl acetate:triethylamine to 47.5:47.5:5 i-hexane:ethyl acetate:triethylamine gradient. The fractions containing product were combined and evaporated in vacuo to give the subtitled compound as a clear oil. Yield 0.8 g.

Provenance & Evidence