4-Methylmorpholine → L-Glutamine, N2-((1,1-dimethylethoxy)carbonyl)-

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Reaction Steps

Boc-Gln-AMC was prepared by coupling anhydrous Boc-Gln-OH (7.03 g, 28.5 mmol) to 7-amino-4-methylcoumarin (AMC) by the mixed anhydride coupling procedure outlined above. First, a solution of a mixed anhydride of Boc-Gln-OH was prepared by reacting Boc-Gln-OH with an equivalent of N-methylmorpholine and an equivalent of isobutyl chloroformate, and the resulting solution was added to AMC (5.00 g, 28.5 mmol) dissolved in 30 mL DMF. After the resulting reaction was complete, the reaction mixture was filtered and the filtrate concentrated. Product (5 g) was separated from the filtrate and dissolved in 75 mL hot methanol. This solution was then concentrated to about 30 mL and cooled. Solid AMC was separated from the solution by filtration, and the remaining filtrate was further concentrated to a volume of about 5 mL. This concentrated solution was then diluted with 30 mL chloroform, and the resulting solution applied to a 4 cm column containing about 30 g silica gel. Residual AMC was eluted from the column with additional chloroform, and product Boc-Gln-AMC (0.97 g) was then recovered from the column by elution with 2% methanol in chloroform. Recrystallization of product from methanol provided 0.46 g of purified Boc-Gln-AMC, mp 260.5-207°. TLC with methanol:chloroform (1:9) indicated a single spot, Rf 0.28.

Provenance & Evidence