Acetone → [4-acetylamino-3-(4-chlorophenylsulfanyl)-2-methyl-1H-indol-1-yl]acetic acid ethyl ester

HRID 1516993Notes

Reaction equation

HRID 1516993 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([S:8][C:9]2[C:17]3[C:12](=[CH:13][CH:14]=[CH:15][C:16]=3[NH:18][C:19](=[O:21])[CH3:20])[NH:11][C:10]=2[CH3:22])=[CH:4][CH:3]=1.C(=O)([O-])[O-].[K+].[K+].CC(C)=O.Br[CH2:34][C:35]([O:37][CH2:38][CH3:39])=[O:36]>O>[C:19]([NH:18][C:16]1[CH:15]=[CH:14][CH:13]=[C:12]2[C:17]=1[C:9]([S:8][C:5]1[CH:4]=[CH:3][C:2]([Cl:1])=[CH:7][CH:6]=1)=[C:10]([CH3:22])[N:11]2[CH2:34][C:35]([O:37][CH2:38][CH3:39])=[O:36])(=[O:21])[CH3:20]

Participants

6

Reactant 4

HCID 180AcetoneHCID 7748Ethyl bromoacetateHCID 11430Potassium CarbonateHCID 58160349N-[3-(4-chlorophenylsulfanyl)-2-methyl-1H-indol-4-yl]acetamide

Product 1

HCID 11546184[4-acetylamino-3-(4-chlorophenylsulfanyl)-2-methyl-1H-indol-1-yl]acetic acid ethyl ester

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A mixture of N-[3-(4-chlorophenylsulfanyl)-2-methyl-1H-indol-4-yl]acetamide (1.0 g, 3.0 mmol), anhydrous potassium carbonate (0.63 g, 4.6 mmol), acetone (10 mL) and ethyl bromoacetate (0.50 mL, 4.5 mmol) was heated under reflux for 1.5 h then cooled to r.t. and left stirring at this temperature overnight. After heating under reflux for an additional 1 h, the mixture was cooled to r.t. Water (2×10 mL) was added, the solid product was collected by filtration, washed with water (10 mL), then dried in a vacuum oven at 40° C. to afford the title compound as an off-white solid; 1.16 g (92%); purity 95.4 area % by HPLC; m/z: 417/419 (MH+); 1H-NMR: 9.52 (1H, s), 7.45 (1H, d, J=7.9 Hz), 7.33 (1H, d, J=8.2 Hz), 7.29 (2H, d, J=8.6 Hz), 7.11 (1H, t, J=8.0 Hz), 6.97 (1H, d, J=8.6 Hz), 5.24 (2H, s), 4.18 (2H, q, J=7.1 Hz), 2.39 (3H, s), 1.86 (3H, s), 1.22 (3H, t, J=7.1 Hz).

Workup

  1. temperaturewas heated
  2. temperatureunder reflux for 1.5 h
  3. waitleft
  4. temperatureAfter heating
  5. temperatureunder reflux for an additional 1 h
  6. temperaturethe mixture was cooled to r.t
  7. filtrationthe solid product was collected by filtration
  8. washwashed with water (10 mL)
  9. customdried in a vacuum oven at 40° C.

Sources & evidence

ORD record
ord-f4c3678cab604a0ca1b83131666400e9
Source dataset
uspto-grants-2012_07
Patent number
US08227622B2

Reaction notes

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