Triethyl phosphite → diethyl [1-hydroxy-4-(2-methyl-7-nitro-1-oxo-2,3-dihydro-1H-isoindol-4-yl)cyclohex-3-en-1-yl]phosphonate

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Reaction Steps

2-methyl-7-nitro-4-(4-oxocyclohex-1-en-1-yl)-2,3-dihydro-1H-isoindol-1-one (Compound 193D) was dissolved in DCM (10 mL), then triethyl phosphite (520 mg, 3.1 mmol) and 1N HCl/Et2O (3.1 mmol, 3.1 mL) were added at 0° C. under nitrogen. The resulting mixture was slowly warmed to rt and stirred at rt overnight. The solvent was evaporated, and the residue was purified by silica gel chromatography (ISCO Combi-flash system, eluting with 0-10% MeOH/DCM) to give the title compound as a yellow solid, 470 mg, 71% yield (over two steps). 1H NMR (CDCl3): 1.39 (t, J=7.1 Hz, 6H), 2.02 (m, 1H), 2.20 (m, 1H), 2.30-2.47 (m, 2H), 2.65-2.83 (m, 2H), 3.20 (s, 3H), 4.21-4.29 (m, 4H), 4.42, 4.48 (AB, JAB=18.0 Hz, 2H), 5.86 (m, 1H), 7.48 (d, J=8.3 Hz, 1H), 7.71 (d, J=7.3 Hz, 1H). MS (ES+): m/z=425.12 [MH+]. HPLC: tR=3.19 min (ZQ3, polar—5 min).

Provenance & Evidence