Carbodiimide → (S)-2-amino-4-hydroxy-N-(5-(3-(piperidin-4-yloxy)phenyl)pent-4-ynyl)butanamide

Participants

Reaction Steps

To a solution of N-Boc-L-Homoserine (16 mg, 0.075 mmol, 1.5 eq) and HOBT hydrate (12 mg, 0.085 mmol, 1.7 eq) in DMF (2 mL) was added PS-carbodiimide (also known as N-Cyclohexylcarbodiimide-N′-propoxymethyl polystyrene, purchased from Biotage) (80 mg, 1.25 mmol/g resin, 0.1 mmol, 2.0 eq). After 10 minutes, a solution of tert-butyl 4-(3-(5-aminopent-1-ynyl)phenoxy)piperidine-1-carboxylate (0.25 mL of a 0.2 M solution in DCM, 0.05 mmol, 1.0 eq) was added and the resulting solution stirred overnight. To the resulting solution was then added MP-carbonate resin (95 mg, 2.64 mmol/g resin, 0.25 mmols, 5 eq), the suspension stirred 2 hrs, filtered, the resin washed with DCM and the filtrate concentrated by rotovap. The residue was taken up in 20% TFA/DCM (2 mL) and stirred 1 hr, methanol (1 mL) was added, and the resulting solution concentrated by rotovap. The resulting residue was purified by HPLC to yield (S)-2-amino-4-hydroxy-N-(5-(3-(piperidin-4-yloxy)phenyl)pent-4-ynyl)butanamide as a gum. ESI-MS (m/z): Calculated for C20H29N3O3: 360.2 (M+1); Measured: 360.2.

Provenance & Evidence