Diisopropylcarbodiimide → HCID 178454160, compound

Participants

Reaction Steps

A suspension of 8.6 g (5 mmol) of oxime resin (described in W. F. DeGrado and E. T. Kaiser, J. Org. Chem., 47, 3258 (1982)), 2.652 g of BOC-L-phenylalanine and 5.0 ml of 2.0M diisopropylcarbodiimide (DIC) in 96 ml of CH2Cl2 was shaken gently for 3days. The resulting resin was filtered off and washed successively with 5×100 ml of 2:1 CH2Cl2 /C2H5OH, 3×100 ml CH3OH and dried. Unreacted sites were blocked by shaking for 15 ml with 6.05 ml of C6H5COCl and 9.05 ml of diisopropylethylamine (DIEA) in 100 ml of CH2Cl2. The solid was filtered off and vacuum dried to give 10.1 g of BOC-L-Phe-oxime resin. A 4.69 g portion (1.37 mmol) of the resin was coupled successively with 2.6 mmoles of the symmetric anhydrides of BOC-L-proline (3 h) and BOC-L-tyrosine (t-butyl ether) (17 h) using a Beckman 990B synthesizer and the program of Nakagawa and Kaiser, described in J. Org. Chem., 48, 678 (1983). The symmetric anhydride was prepared by treating 7.2 mmoles of the corresponding BOC-amino acid (Bachem, Switzerland) in 38 ml of CH2Cl2 and 10 ml of dimethylformamide (DMF) with 3.6 ml of 1M DIC in CH2Cl2 at 0°. Note that there is no neutralization step in this program; after the addition of 3.6 mmole of the preformed BOC symmetric anhydride, 4.6 ml of 10% DIEA in CH2Cl2 was added. The resulting BOC-Tyr(tBu)-Pro-Phe-resin was washed with ethanol and after vacuum drying weighed 5.17 g. (Amino acid analysis found: Tyr, 0.301; Pro, 0.272; Phe. 0.292 mmol/g).

Provenance & Evidence