Sodium hydride → {9-[(3-Methylphenyl)methyl)-2-methyl-5-carbamoylcarbazol-4-yl}oxyacetic acid, methyl ester

HRID 51330Notes

Reaction equation

HRID 51330 reaction equation
[H-].[Na+].[CH3:3][C:4]1[CH:5]=[C:6]([CH2:10][N:11]2[C:23]3[CH:22]=[C:21]([CH3:24])[CH:20]=[C:19]([OH:25])[C:18]=3[C:17]3[C:12]2=[CH:13][CH:14]=[CH:15][C:16]=3[C:26](=[O:28])[NH2:27])[CH:7]=[CH:8][CH:9]=1.Br[CH2:30][C:31]([O:33][CH3:34])=[O:32]>CN(C=O)C.C1COCC1.C(OCC)(=O)C>[CH3:3][C:4]1[CH:5]=[C:6]([CH2:10][N:11]2[C:23]3[CH:22]=[C:21]([CH3:24])[CH:20]=[C:19]([O:25][CH2:30][C:31]([O:33][CH3:34])=[O:32])[C:18]=3[C:17]3[C:12]2=[CH:13][CH:14]=[CH:15][C:16]=3[C:26](=[O:28])[NH2:27])[CH:7]=[CH:8][CH:9]=1

Participants

7

Reactant 3

HCID 24758Sodium hydrideHCID 60984Methyl bromoacetateHCID 227401829-[(3-Methylphenyl)methyl]-2-methyl-4-hydroxy-5-carbamoyl carbazole

Product 1

HCID 86756258{9-[(3-Methylphenyl)methyl)-2-methyl-5-carbamoylcarbazol-4-yl}oxyacetic acid, methyl esterYield 76%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

60% Sodium hydride in mineral oil (79.8 mg, 2.0 mM) was added to a solution of 9-[(3-methylphenyl)methyl]-2-methyl-4-hydroxy-5-carbamoyl carbazole (0.55 g, 1.60 mM) in 56 mL DMF and 12 ml THF. After 10 minutes, methyl bromoacetate (0.20 ml, 2.16 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 methylene chloride/acetone gradient) to afford 0.51 g (76%) of {9-[(3-methylphenyl)methyl]-2-methyl-5-carbamoylcarbazol-4-yl}oxyacetic acid, methyl ester. 1H NMR (DMSO-d6) δ7.5 (m, 2H), 7.35 (dd, J=8 and 8 Hz, 1H), 7.2-7.1 (m, 2H), 7.05-6.95 (m, 4H), 6.85 (d, J=8 Hz, 1H), 6.45 (s, 1H), 5.6 (s, 2H), 4.9 (s, 2H), 3.75 (s, 3H), 2.4 (s, 3H), 2.2 (s, 3H). MS (FD) m/e 400, 417.

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 methylene chloride/acetone gradient)

Sources & evidence

ORD record
ord-f219cf493c4741a288a77ed2efa50788
Source dataset
uspto-grants-2004_03
Patent number
US06713645B1

Reaction notes

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