Benzhydrylamine → Boc-Cys(Dmb) Benzhydrylamine

Participants

Reaction Steps

A suspension of benzhydrylamine resin (24 g, 0.54 meq/g, 12.96 mmol) was placed in a reaction vessel clamped to a manual shaker and successively washed with methylene chloride (CH2Cl2 ; 4×250 ml), 10% diisopropylethylamine (DIEA; 1×250 ml, 10 min) and CH2Cl2 (1×250 ml). The procedure was repeated, and the resin was then washed with methanol (MeOH; 2×250 ml), CH2Cl2 (2×250 ml) and dimethylformamide (DMF; 4×250 ml). A solution of Boc-Cys(Dmb)-OH (13.27 g, 38.9 mmol) in DMF (200 ml) was added and shaken for 5 min. To the slurry was then added a solution of benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphate (BOP; 17.20 g, 38.9 mmol) in DMF (50 ml) followed immediately by the addition of DIEA (20.32 ml, 116.6 mmol) and shaking continued for 150 minutes. An aliquot of resin was removed (100 mg) and assayed by the Gisin test (Anal. Chim. Acta 58, 248-249 [1972]). The substitution was found to be 0.23 meq/g-resin. The total resin was filtered, washed with DMF (2×250 ml), CH2Cl2 (2×250 ml) and recoupled with Boc-Cys(Dmb) (13.27 g, 38.9 mmol) and 1,3-dicyclohexylcarbodiimide (DCC; 8.02 g, 38.2 mmol) in CH2Cl2 (250 ml) for 24 hours. The Gisin test was repeated on a 100 mg resin aliquot and the loading determined to be 0.36 mmol/g-resin. The resin was suspended in 150 ml of pyridine and 150 ml acetic anhydride, shaken for 1 hour, filtered and washed with CH2Cl2 (2×250 ml), MeOH (2×250 ml), CH2Cl2 (2×250 ml) and dried in vacuo.

Provenance & Evidence