Sulfuric Acid → (2S)-2-({[(9H-fluoren-9-yl)methoxy]carbonyl}amino)-4-[(triphenylmethyl)carbamoyl]butanoic acid

Participants

Reaction Steps

A mixture of 7.4 g of Fmoc-Gln-OH (20 mmol) and 10.4 g of triphenylmethanol (40 mmol) in 300 ml of acetic acid is stirred at 100° for 10 minutes. After the addition of 0.1 ml of concentrated sulfuric acid the whole is stirred at 100° for a further 15 minutes, a clear yellow solution forming. This is concentrated by evaporation under reduced pressure at 60°, and the residue is dried under reduced pressure for 10 minutes. The solid residue is dissolved in 60 ml of acetic acid at 60°, left at 60° for 20 minutes, then 2 ml of acetic anhydride (20 mmol) are added and after 1 hour at 60° the whole is concentrated by evaporation under reduced pressure. The oily residue is dried for 10 minutes at 60°, then dissolved in 100 ml of acetic acid and introduced dropwise into 500 ml of ice-cold water. The precipitate is isolated by filtration, washed well with water and dissolved in ethyl acetate; the aqueous phase is separated off and the organic phase is washed with a saturated aqueous sodium chloride solution. After drying over sodium sulfate, the organic solution is concentrated to dryness by evaporation, the residue is dissolved in 50 ml of 1,2-dichloroethane and applied to 100 g of silica gel; elution is carried out with 1,2-dichloroethane and with 1,2-dichloroethane containing 2%, then 4%, methanol. The fractions containing the Fmoc-Gln(Trt)-OH are concentrated by evaporation under reduced pressure, and the product is crystallised from a mixture of ethyl acetate and diisopropyl ether, m.p. from 125°.

Provenance & Evidence