Hydrochloric Acid → N1-(1(S)-benzyl-2-hydroxyethyl)-3(R)-(3-biphenyl-4-yl-1H-pyrrol-1-yl)-N4-hydroxysuccinamide

Participants

Reaction Steps

To a solution of N-(1(S)-benzyl-2-hydroxyethyl)-3(R)-(3-(biphenyl-4-yl)-1H-pyrrol-1-yl)succinamic acid (prepared as described in Example 1(a); 61 mg, 0.130 mmol) in CHCl3 (2 mL) was added in succession NMM (44 μL, 0.39 mmol), benzotriazole-1-yloxy-tris-1H-pyrrolidino-phosphonium hexafluorophosphate (PyBOP, 203 mg, 0.390 mmol), and hydroxylamine hydrochloride (27 mg, 0.390 mmol). After 20 hours at ambient temperature, 10% aqueous HCl (2 mL) and saturated aqueous NH4Cl (10 mL) were added, and the resultant mixture extracted with CHCl3 (15 mL) three times. The combined organic layers were washed with saturated aqueous NH4Cl (10 mL), dried over Na2SO4, and evaporated to provide a yellow solid, which was purified via flash column chromatography with 1% HOAc/10% MeOH/CHCl3 as eluant. Subsequent radial chromatography with a 1% HOAc/5-10%MeOH/CH2Cl2 stepwise gradient eluant and azeotropic removal of HOAc with n-heptane gave 9 mg (14%) of N1 -(1(S)-benzyl-2-hydroxyethyl)-3(R)-(3-biphenyl-4-yl-1H-pyrrol-1-yl)-N4 -hydroxysuccinamide as a yellow solid. 1H NMR (CD3OD): ∂ 6.90-6.79 (m, 1H), 6.58-6.76 (m, 1H), 5.18-5.02 (m, 1H), 4.19-4.01 (m, 1H), 3.00-2.84 (m, 1H), 2.84-2.70 (m, 3H). IR (CHCl3): 3244, 3018, 1659, 1208, 1201 cm-1. HRFABMS: Calculated for C29H30N3O4 (M+H+): 483.2158. Found: 483.2139. Anal. Calculated for C29H30N3O4.NH2OH.0.2 CHCl3.0.25 H2O: C, 64.35; H, 6.05; N, 10.28. Found: C, 64.13; H, 5.69; N, 10.56.

Provenance & Evidence