Methyl bromoacetate → {9-[(2-Fluorophenyl)methyl]-5-carbamoylcarbazol-4-yl}oxyacetic acid, methyl ester

HRID 51373Notes

Reaction equation

HRID 51373 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH2:8][N:9]1[C:21]2[CH:20]=[CH:19][CH:18]=[C:17]([OH:22])[C:16]=2[C:15]2[C:10]1=[CH:11][CH:12]=[CH:13][C:14]=2[C:23](=[O:25])[NH2:24].Br[CH2:27][C:28]([O:30][CH3:31])=[O:29]>CN(C=O)C.C(OCC)(=O)C>[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH2:8][N:9]1[C:21]2[CH:20]=[CH:19][CH:18]=[C:17]([O:22][CH2:27][C:28]([O:30][CH3:31])=[O:29])[C:16]=2[C:15]2[C:10]1=[CH:11][CH:12]=[CH:13][C:14]=2[C:23](=[O:25])[NH2:24]

Participants

5

Reactant 2

HCID 60984Methyl bromoacetateHCID 227385489-[(2-Fluorophenyl)methyl]-4-hydroxy-5-carbamoyl carbazole

Product 1

HCID 86756263{9-[(2-Fluorophenyl)methyl]-5-carbamoylcarbazol-4-yl}oxyacetic acid, methyl esterYield 115.4%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

40% Methanolic Triton B (0.14 mL, 0.31 mM) was added to a solution of the 9-[(2-fluorophenyl)methyl]-4-hydroxy-5-carbamoyl carbazole (51.9 mg, 0.155 mM) in 5 mL DMF at room temperature. After 3 minutes, methyl bromoacetate (110.5 mg, 0.72 mM) was added and the resultant mixture stirred at room temperature for 20 hours. The mixture was diluted with ethyl acetate, washed four times with H2O, once with saturated brine, dried over magnesium sulfate, filtered, and concentrated. The residue was purified by column chromatography on silica gel (elution with gradient methylene chloride/ethyl acetate) to afford 72.8 mg (71%) of the {9-[(2-fluorophenyl)methyl]-5-carbamoylcarbazol-4-yl}oxyacetic acid, methyl ester as a white solid. 1H NMR (DMSO-d6) δ7.65 (d, 1H, J=8 Hz), 7.5 (s, 1H), 7.4-7.2 (m, 5H), 7.15 (s, 1H), 7.1 (d, 1H, J=8 Hz), 7.05 (t, 1H, J=8 Hz), 6.7 (t, 1H, J=8 Hz), 6.55 (d, 1H, J=8 Hz), 5.7 (s, 2H), 4.85 (s, 2H), and 3.7 (s, 3H). IR (CHCl3, cm−1) 3436, 1763, 1675, 1457, 1327, 1208, 1198, 1150, 1102, 772, 756, and 719. MS (FD) m/e 407.

Workup

  1. washwashed four times with H2O
  2. dry with materialonce with saturated brine, dried over magnesium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe residue was purified by column chromatography on silica gel (elution with gradient methylene chloride/ethyl acetate)

Sources & evidence

ORD record
ord-c8dd2a5e27ed4f60b04bd30bf127190c
Source dataset
uspto-grants-2004_03
Patent number
US06713645B1

Reaction notes

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