Sodium hydride → (R)-tert-butoxycarbonylamino-{4-[2-(tetrahydropyran-2-yloxy)-ethoxy]-phenyl}-acetic acid

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Reaction Conditions

Reaction Steps

(R)-tert-butoxycarbonylamino-(4-hydroxy-phenyl)-acetic acid (2.67 g, 10 mmol) (Salituro, G. M.; Townsend, C. A. J. Am. Chem. Soc. 1990, 112, 760-770) was dissolved in N,N-dimethylformamide (70 mL) in an ice bath. Sodium hydride (0.88 g, 60% in mineral oil, 22 mmol) was added in small portions. The mixture was warmed up to 10° C. for 1 hour. 2-(2-Bromo-ethoxy)-tetrahydropyran (1.7 mol, 11 mmol) in N,N-dimethylformamide (20 mL) was added drop wise. The reaction mixture was stirred for 24 hours and then diluted with ice/water. The mixture was extracted with ethyl acetate. The aqueous layer was cooled in an ice bath and acidified using 1.5 M aqueous potassium hydrogen sulfate to pH=2-3. The resulting mixture was extracted with ethyl acetate (5×), washed with water (5×), brine and dried over sodium sulfate. Filtration and evaporation of the solvents gave (R)-tert-butoxycarbonylamino-{4-[2-(tetrahydropyran-2-yloxy)-ethoxy]-phenyl}-acetic acid as a solid white foam (3.2 g, 82%).

Provenance & Evidence