Methyl Salicylate → (2S,4R)-2-(2,4,5-trifluoro-benzyloxymethyl)-4-tritylsulfanyl-pyrrolidine-1-carboxylic acid 2-methoxycarbonyl-phenyl ester

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Reaction Steps

A solution of 0.07 ml (0.55 mmol) trichloromethyl-chloroformate in 7 ml CH2Cl2 was treated at 0° C. with 0.13 ml (1.1 mmol) quinoline and after 15 min with 0.52 g (1 mmol) (2S,4R)-2-(2,4,5-trifluoro-benzyloxymethyl)-4-tritylsulfanyl-pyrrolidine in 7 ml CH2Cl2. After 2 h at 0° C. the CH2Cl2 was evaporated. The residue was dissolved in 15 ml THF, treated at 0° C. with 0.27 ml (2.1 mmol) methyl salicylate, 96 mg (2.4 mmol) of 55% NaH and 166 mg (1 mmol) of KI. The reaction was stirred at room temperature over night, cooled (0° C.) and after the addition of 44 mg (1 mmol) of 55% NaH refluxed for 3 h. The reaction was partitioned between aqueous 10% KHSO4/EtOAc (3×300). The organic phases were washed with aqueous 10% NaCl, dried (Na2SO4) and evaporated. Flash chromatography on silica gel (Hexane/EtOAc 9:1) gave 0.48 g (69%) (2S,4R)-2-(2,4,5-trifluoro-benzyloxymethyl)-4-tritylsulfanyl-pyrrolidine-1-carboxylic acid 2-methoxycarbonyl-phenyl ester, MS: 698 (MH+).

Provenance & Evidence