1,4-Cyclohexadiene → HCID 44409723, compound

HRID 2054762Notes

Reaction equation

HRID 2054762 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[C:9]1[CH2:13][N:12]([C:14]([C@@H:16]([NH:21][C:22](=[O:45])[O:23][CH2:24][CH2:25][O:26][P:27]([O:37]CC2C=CC=CC=2)([O:29]CC2C=CC=CC=2)=[O:28])[C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[C@H:11]([C:46]2[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=2)[CH:10]=1.C1CC=CCC=1>[Pd].CO>[F:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[C:9]1[CH2:13][N:12]([C:14]([C@@H:16]([NH:21][C:22](=[O:45])[O:23][CH2:24][CH2:25][O:26][P:27]([OH:37])([OH:29])=[O:28])[C:17]([CH3:20])([CH3:18])[CH3:19])=[O:15])[C@H:11]([C:46]2[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=2)[CH:10]=1

Participants

5

Reactant 2

HCID 123431,4-CyclohexadieneHCID 59656621HCID 59656621, compound

Product 1

HCID 44409723HCID 44409723, compound

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalyst2×HCID 887MethanolSolvent

Procedure

2-{[bis(benzyloxy)phosphoryl]oxy}ethyl (1S)-1-{[(2S)-4-(2,5-difluorophenyl)-2-phenyl-2,5-dihydro-1H-pyrrol-1-yl]carbonyl}-2,2-dimethylpropylcarbamate (9-2, 11 mg, 0.015 mmol, 1 equiv), 1,4-cyclohexadiene (1 mL, excess) and 10% Pd/C (5 mg) were added to methanol (4 mL) and the mixture was stirred under a nitrogen atmosphere. After 30 minutes another 5 mg of 10% Pd/C was added and stirring was continued for an additional hour. The reaction was filtered and the filtrate concentrated. The residue was purified by reverse phase LC (H2O/CH3CN gradient w/0.1% TFA present) to give 2-(phosphonooxy)ethyl (1S)-1-{[(2S)-4-2,5-difluorophenyl)-2-phenyl-2,5-dihydro-1H-pyrrol-1-yl]carbonyl}-2,2-dimethylpropylcarbamate (9-3) as a colorless foam. 1H NMR (500 MHz, CDCl3) major rotamer: δ 7.34-7.20 (m, 5H), 7.12-6.92 (m, 3H), 6.38 (s, 1H), 5.93 (bs, 1H), 5.21 (d, 1H, J=14 Hz), 4.91 (d, 1H, J=14 Hz), 4.41 (d, 1H, J=10 Hz), 4.38-3.97 (m, 7H), 0.91 (s, 9H). LRMS m/z (M+H) 539.5 found, 538.2 required.

Workup

  1. stirringstirring
  2. waitwas continued for an additional hour
  3. filtrationThe reaction was filtered
  4. concentrationthe filtrate concentrated
  5. customThe residue was purified by reverse phase LC (H2O/CH3CN gradient w/0.1% TFA present)

Sources & evidence

ORD record
ord-f2c6cfac6375489ea35b0080e795e9dd
Source dataset
uspto-grants-2008_02
Patent number
US07329762B2

Reaction notes

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