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. Addition of 0.1 ml of conc. sulfuric acid is followed by stirring at 100° for a further 15 minutes to produce a clear yellow solution. This is evaporated at 60° under reduced pressure, and the residue is then 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 mixture is evaporated under reduced pressure. The oily residue is dried at 60° for 10 minutes, then dissolved in 100 ml of acetic acid and added dropwise to 500 ml of ice-cold water. The precipitate is filtered off, thoroughly washed 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. The organic solution is dried over sodium sulfate and then evaporated to dryness, and the residue is dissolved in 50 ml of 1,2-dichloroethane and applied to 100 g of silica gel; elution is with 1,2-dichloroethane and 1,2-dichloroethane containing 2%, then 4% methanol. The fractions containing Fmoc-Gln(Trt)-OH are evaporated under reduced pressure, and the product is crystallized from a mixture of ethyl acetate and diisopropyl ether, m.p. above 125°.

Provenance & Evidence