Triethylamine → [2-(2,3-Dihydro-indol-1-yl)-2-oxo-ethyl]-phosphonic acid diethyl ester

Participants

Reaction Conditions

Reaction Steps

Oxalyl chloride (5.96 mL, 68.3 mmol, 1.05 equiv) was added to a solution of diethylphosphonoacetic acid (12.8 g, 65.0 mmol, 1 equiv) and N,N-dimethylformamide (0.03 mL, 0.39 mmol, 0.006 equiv) in benzene (150 mL) at 23° C. The reaction mixture was stirred at 23° C. for 1 hour and then concentrated under reduced pressure. The resulting oil was dissolved in THF (30 mL) and added via cannula to a solution of indoline (7.38 g, 61.9 mmol, 0.95 equiv) and triethylamine (10.9 mL, 78.0 mmol, 1.2 equiv) in THF (200 mL) at 0° C. The reaction mixture was stirred at 0° C. for 15 minutes, and it then was partitioned between 0.5 M HCl (150 mL) and EtOAc (2×150 mL). The combined organic layers were dried over Na2SO4 and concentrated to afford a tan solid. Recrystallization from Et2O provided [2-(2,3-dihydro-indol-1-yl)-2-oxo-ethyl]-phosphonic acid diethyl ester (12.2 g, 63%) as a light brown solid: mp: 97-99° C.; R.function. =0.06 (50% EtOAc in hexanes); IR (cm-1) 3460, 1657, 1597, 1482; 1H NMR (CDCl3) δ 1.35 (t, 6H, J=7.2), 3.14 (d, 2H, J=22.4), 3.22 (d, 2H, J=8.4), 4.15-4.30 (m, 6H), 7.04 (t, 1H, J=7.0), 7.17-7.28 (m, 2H), 8.21 (d, 1H, J=9.0); Anal. (C14H20NO4P) C, H, N.

Provenance & Evidence