Sodium hydride → {9-[(Phenyl)methyl]-2-(4-trifluoromethylphenyl)-5-carbamoylcarbazol-4-yl}oxyacetic acid, methyl ester

HRID 567247Notes

Reaction equation

HRID 567247 reaction equation
[H-].[Na+].[C:3]1([CH2:9][N:10]2[C:22]3[CH:21]=[C:20]([C:23]4[CH:28]=[CH:27][C:26]([C:29]([F:32])([F:31])[F:30])=[CH:25][CH:24]=4)[CH:19]=[C:18]([OH:33])[C:17]=3[C:16]3[C:11]2=[CH:12][CH:13]=[CH:14][C:15]=3[C:34](=[O:36])[NH2:35])[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.Br[CH2:38][C:39]([O:41][CH3:42])=[O:40]>CN(C=O)C.C1COCC1.C(OCC)(=O)C>[C:3]1([CH2:9][N:10]2[C:22]3[CH:21]=[C:20]([C:23]4[CH:28]=[CH:27][C:26]([C:29]([F:32])([F:31])[F:30])=[CH:25][CH:24]=4)[CH:19]=[C:18]([O:33][CH2:38][C:39]([O:41][CH3:42])=[O:40])[C:17]=3[C:16]3[C:11]2=[CH:12][CH:13]=[CH:14][C:15]=3[C:34](=[O:36])[NH2:35])[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1

Participants

7

Reactant 3

HCID 24758Sodium hydrideHCID 60984Methyl bromoacetateHCID 227396819-[(Phenyl)methyl]-2-(4-trifluoromethylphenyl)-4-hydroxy-5-carbamoyl carbazole

Product 1

HCID 86756259{9-[(Phenyl)methyl]-2-(4-trifluoromethylphenyl)-5-carbamoylcarbazol-4-yl}oxyacetic acid, methyl esterYield 84%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

60% Sodium hydride in mineral oil (22 mg, 0.54 mM) was added to a solution of the 9-[(phenyl)methyl]-2-(4-trifluoromethylphenyl)-4-hydroxy-5-carbamoyl carbazole (0.20 g, 0.43 mM) in 15 mL DMF and 3 ml THF. After 7 minutes, methyl bromoacetate (56 μl, 0.59 mM) was added and the resultant mixture stirred at room temperature for 1 hour. The mixture was diluted with ethyl acetate and washed with H2O. The aqueous layer was extracted with ethyl acetate. The combined organic layers were extracted with saturated brine, dried over sodium sulfate, filtered, and concentrated. The residue was purified by column chromatography on silica gel (elution with ethyl acetate) to afford 0.19 g (84%) of the {9-[(phenyl)methyl]-2-(4-trifluoromethylphenyl)-5-carbamoylcarbazol-4-yl}oxyacetic acid, methyl ester. 1H NMR (DMSO-d6) δ 8.0 (d, J=8 Hz, 2H), 7.85 (d, J=8 Hz, 2H), 7.7 (s, 1H), 7.6 (d, J=8 Hz, 1H), 7.6 (bs, 1H), 7.4 (dd, J=8 and 8 Hz, 1H), 7.3-7.1 (m, 6H), 7.1 (d, J=8 Hz, 1H), 7.0 (s, 1H), 5.8 (s, 2H), 5.1 (s, 2H), 3.7 (s, 3H). MS (FD) m/e 516, 533.

Workup

  1. washwashed with H2O
  2. extractionThe aqueous layer was extracted with ethyl acetate
  3. extractionThe combined organic layers were extracted with saturated brine
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified by column chromatography on silica gel (elution with ethyl acetate)

Sources & evidence

ORD record
ord-b58b06311caa405f9bef683697546304
Source dataset
uspto-grants-2001_01
Patent number
US06177440B1

Reaction notes

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