Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphate → 4-{(S)-2-[(E)-3-(5-chloro-2-tetrazol-1-yl-phenyl)-acryloylamino]-3-methoxycarbonyl-propionylamino}-benzoic acid

Participants

Reaction Steps

(S,E)-tert-butyl 4-(2-(3-(5-chloro-2-(1H-tetrazol-1-yl)phenyl)acrylamido)-4-methoxy-4-oxobutanamido)benzoate: 44BA was dissolved in MeOH (50 mL), treated with 5% Pd/C, and placed under hydrogen atmosphere (50 psi). After 12 h, the mixture was filtered through a plug of Celite® and the filter-cake was rinsed several times with MeOH. The combined filtrate was concentrated. The resulting oil was dissolved in THF (50 mL) and then (E)-3-(5-chloro-2-(1H-tetrazol-1-yl)phenyl)acrylic acid (0.89 g, 3.56 mmol), BOP (1.57 g, 3.56 mmol), and TEA (1.48 mL, 10.67 mmol) were added at 25° C. with stirring. After 2 h, the reaction mixture was diluted with EtOAc, washed with water and then brine, dried over sodium sulfate, filtered, and concentrated. Purification by flash chromatography (40 g column; (100% hexane/0% EtOAC to 0% hexane over 30 min) afforded 44BB (1.8 g, 55%) as a white solid. LCMS m/z 555 [M+H]+.

Provenance & Evidence