Methyl bromoacetate → 9-[(Phenyl)methyl]-5-carbamoylcarbazol-4-yloxyacetic acid, methyl ester

HRID 585588Notes

Reaction equation

HRID 585588 reaction equation
[C:1]1([CH2:7][N:8]2[C:20]3[CH:19]=[CH:18][CH:17]=[C:16]([OH:21])[C:15]=3[C:14]3[C:9]2=[CH:10][CH:11]=[CH:12][C:13]=3[C:22](=[O:24])[NH2:23])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.Br[CH2:26][C:27]([O:29][CH3:30])=[O:28]>CN(C=O)C.C(OCC)(=O)C>[C:1]1([CH2:7][N:8]2[C:20]3[CH:19]=[CH:18][CH:17]=[C:16]([O:21][CH2:26][C:27]([O:29][CH3:30])=[O:28])[C:15]=3[C:14]3[C:9]2=[CH:10][CH:11]=[CH:12][C:13]=3[C:22](=[O:24])[NH2:23])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1

Participants

5

Reactant 2

HCID 60984Methyl bromoacetateHCID 223377189-[(Phenyl)methyl]-4-hydroxy-5-carbamoyl carbazole

Product 1

HCID 101783439-[(Phenyl)methyl]-5-carbamoylcarbazol-4-yloxyacetic acid, methyl esterYield 88.4%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

40% Methanolic Triton B (0.11 mL, 0.24 mM) was added to a solution of the 9-[(phenyl)methyl]-4-hydroxy-5-carbamoyl carbazole (70 mg, 0.22 mM) in 20 mL DMF at 0° C. After 15 minutes, methyl bromoacetate (70 mg, 0.44 mM) was added and the resultant mixture stirred at room temperature for 5 hours. The mixture was diluted with ethyl acetate, washed with 1 N HCl, H2O, and saturated brine, dried over magnesium sulfate, filtered, and concentrated. The residue was combined with the crude material derived from a similar run utilizing 45 mg (0.14 mM [0.36 mM total]) of 9-[(phenyl)methyl]-4-hydroxy-5-carbamoyl carbazole. The combined residues were purified by column chromatography on silica gel (elution with ethyl acetate) to afford 76 mg (54%) of the {9-[(phenyl)methyl]-5-carbamoylcarbazol-4-yl}oxyacetic acid, methyl ester as a white solid. 1H NMR (DMSO-d6) δ 7.65 (d, 1H, J=8 Hz), 7.5 (br s, 1H), 7.4-7.15 (m, 9H), 7.1 (d, 1H, J=8 Hz), 6.6 (d, 1H, J=8 Hz), 5.7 (s, 2H), 4.9 (s, 2H), and 3.75 (s, 3H). IR (KBr, cm−1) 3367, 3200, 1760, 1643, 1579, 1496, 1452, 1427, 1216, 1157, 772, and 716. MS (FD) m/e 388.

Workup

  1. washwashed with 1 N HCl, H2O, and saturated brine
  2. dry with materialdried over magnesium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe combined residues were purified by column chromatography on silica gel (elution with ethyl acetate)

Sources & evidence

ORD record
ord-00df889781f24534a25061254817e7f3
Source dataset
uspto-grants-2005_08
Patent number
US06933313B2

Reaction notes

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