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

HRID 511425Notes

Reaction equation

HRID 511425 reaction equation
[CH3:1][N:2]1[CH2:10][C:9]2[C:4](=[C:5]([N+:18]([O-:20])=[O:19])[CH:6]=[CH:7][C:8]=2[C:11]2[CH2:16][CH2:15][C:14](=[O:17])[CH2:13][CH:12]=2)[C:3]1=[O:21].[P:22]([O:29]CC)([O:26][CH2:27][CH3:28])[O:23][CH2:24][CH3:25].Cl.CCOCC>C(Cl)Cl>[OH:17][C:14]1([P:22](=[O:29])([O:26][CH2:27][CH3:28])[O:23][CH2:24][CH3:25])[CH2:15][CH2:16][C:11]([C:8]2[CH:7]=[CH:6][C:5]([N+:18]([O-:20])=[O:19])=[C:4]3[C:9]=2[CH2:10][N:2]([CH3:1])[C:3]3=[O:21])=[CH:12][CH2:13]1

Participants

5

Reactant 3

HCID 31215Triethyl phosphiteHCID 10953452Ether hydrochlorideHCID 672543172-methyl-7-nitro-4-(4-oxocyclohex-1-en-1-yl)-2,3-dihydro-1H-isoindol-1-one2×

Product 1

HCID 86654038diethyl [1-hydroxy-4-(2-methyl-7-nitro-1-oxo-2,3-dihydro-1H-isoindol-4-yl)cyclohex-3-en-1-yl]phosphonateYield 71%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

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).

Workup

  1. customThe solvent was evaporated
  2. customthe residue was purified by silica gel chromatography (ISCO Combi-flash system, eluting with 0-10% MeOH/DCM)

Sources & evidence

ORD record
ord-2339638bcab54ce38c19165267de6a79
Source dataset
uspto-grants-2015_08
Patent number
US09096624B2

Reaction notes

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