Triethylamine → (9-(2-Chloro-3-(2-hydroxyethyl)benzyl)-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)(2-ethylthiazol-4-yl)methanone

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Reaction Steps

To a suspension of 2-chloro-3-(2-hydroxyethyl)benzaldehyde [Aromatic Intermediate 11] (1.5 g) and (2-ethylthiazol-4-yl)(1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)methanone trifluoroacetate [Example 26, step b] (4.25 g) in tetrahydrofuran (50 mL) was added triethylamine (2.5 mL) in one portion. The mixture was stirred for 0.5 h, sodium triacetoxyborohydride (2.58 g) was then added in one portion and the resultant solution was stirred for 2 h. The reaction mixture was partitioned between ethyl acetate (100 mL) and saturated sodium bicarbonate solution (50 mL). The mixture was shaken vigorously for 10 min and the layers were separated. The aqueous phase was extracted with ethyl acetate (100 mL). The combined organic solutions were washed with brine, dried over sodium sulphate, filtered and evaporated. The residue was purified by flash silica chromatography using 95:5 ethyl acetate:triethylamine as solvent. The fractions containing the product were combined and evaporated to give the subtitled compound as a clear oil. Yield 3.40 g.

Provenance & Evidence