Citric Acid → (-)-{[(1R)-3-{[5-(4-methoxyphenyl)-6-phenylfuro[2,3-d]pyrimidin-4-yl]oxy}-1-methylpropyl]oxy}acetic acid tert.-butyl ester

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Reaction Conditions

Reaction Steps

Put 455 mg (2.23 mmol) {[(3R)-3-hydroxybutyl]oxy}acetic acid tert.-butyl ester (which contains up to approx. 10% {[(1R)-3-hydroxy-1-methylpropyl]oxy}acetic acid tert.-butyl ester) under argon in 5 ml THF and cool to 0° C. Add 1.15 ml (2.23 mmol) of a 2 M solution of phosphazene base P2-tert.-butyl in THF and stir for a further 10 min at RT. Then cool to 0° C. again. Add 500 mg (1.49 mmol) 4-chloro-5-(4-methoxyphenyl)-6-phenylfuro[2,3-d]pyrimidine and stir overnight at RT. Then dilute with water, acidify with 10% aqueous citric acid solution and extract twice with ethyl acetate. Combine the ethyl acetate phases and wash once with satd. sodium chloride solution. Dry over magnesium sulphate and concentrate by evaporation. Purify the residue by chromatography on silica gel (solvent: cyclohexane/ethyl acetate 9:1). 450 mg (60.1% of theor.) of the target compound is obtained. 75 mg (9.0% of theor.) of (−)-{[(1R)-3-{[5-(4-methoxyphenyl)-6-phenylfuro[2,3-d]pyrimidin-4-yl]oxy}-1-methylpropyl]oxy}acetic acid tert.-butyl ester is isolated as by-product (see Example 77).

Provenance & Evidence