Urea → Trityl-leucine amide

Participants

Reaction Steps

In the preparation of the urea of aniline and leucine methyl amide, 100 mg of p-methylbenzhydrylamine (MBHA) resin (0.81 meq/g, 100-200 mesh) was contained within a sealed polypropylene mesh packet as used in simultaneous multiple synthesis as described in Houghten, (Proc. Natl. Acad. Sci. USA 82:5131, 1985). Following neutralization (1 min) with 5% diisopropylethylamine (DIEA) in dichloromethane (DCM) (3×5 ml), the resin was washed with DCM (3×5 ml). The resin packet was added to a solution of tert-butyloxycarbonyl-L-leucine (Boc-Leu) (111 mg, 0.48 meq) and 1-hydroxybenzotriazole (65 mg, 0.48 meq) in dimethylformamide (DMF) (2.4 ml) in a 10 ml polypropylene bottle. Following addition of 2.4 ml 0.2 M diisopropylcarbodiimide (DICI) in DMF, the resin was shaken on a reciprocation shaker for 1.5 h. The resin was then washed with DMF (3×5 ml) and DCM (3×5 ml). The oc protecting group was then removed by treatment with 55% trifluoroacetic acid in DCM for 30 min. The resin was then washed with DCM (2×5 ml), isopropanol (IPA, 3×5ml), DCM (3×5 ml), neutralized with 5%DIEA in DCM (3×5 ml), and washed with DCM (2×5 ml). The resin packet was then shaken overnight (16 h) in 5 ml of 0.1 M trityl chloride in DCM/DMF (9:1) in the presence of DIEA. Completeness of the trityl coupling was verified using the bromophenol blue color test as described in Krchnak et al., (Coll. Czech. Chem. Commun. 53:2542, 1988), and repeated as necessary.

Provenance & Evidence