3-Acetylamino-7-chloro-2-[(N-methoxy-N-methylamino)carbonyl]indole → 3-Acetylamino-2-benzoyl-7-chloroindole

HRID 379915Notes

Reaction equation

HRID 379915 reaction equation
[C:1]([NH:4][C:5]1[C:13]2[C:8](=[C:9]([Cl:14])[CH:10]=[CH:11][CH:12]=2)[NH:7][C:6]=1[C:15](N(OC)C)=[O:16])(=[O:3])[CH3:2].[C:21]1([Li])[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1>C(OCC)C.O1CCCC1>[C:1]([NH:4][C:5]1[C:13]2[C:8](=[C:9]([Cl:14])[CH:10]=[CH:11][CH:12]=2)[NH:7][C:6]=1[C:15](=[O:16])[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)(=[O:3])[CH3:2]

Participants

4

Reactant 2

HCID 183681463-Acetylamino-7-chloro-2-[(N-methoxy-N-methylamino)carbonyl]indoleHCID 178506676HCID 178506676, compound

Product 1

HCID 183682313-Acetylamino-2-benzoyl-7-chloroindoleYield 26%

Reagents, catalysts & solvents 1

HCID 21868444Ether tetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 3-acetylamino-7-chloro-2-[(N-methoxy-N-methylamino)carbonyl]indole (step 4, 321 mg, 1.08 mmol) in diethyl ether-tetrahydrofuran (1:1, 10 ml) was added phenyl lithium (1M solution in cyclohexane, 5.4 ml, 5.42 mmol) at −78° C. After stirring for 1 h, the mixture was allowed to warm to 0° C. and stirred for an additional 2 h. The mixture was quenched with saturated aqueous ammonium chloride (20 ml) and extracted with ether (150 ml). The organic layer was washed with water (50 ml) and dried (MgSO4). Removal of solvent gave an oily residue. Purification by flash column chromatography eluting with ethyl acetate/hexane (1:3) afforded yellow crystals. Recrystallization from ethyl acetate gave 87 mg, (26%) of the title compound. m.p.: 185-188° C. IR (KBr) ν: 3240, 1690, 1628, 1543, 1375, 1315, 1250, 725 cm1 1H-NMR (CDCl3) δ: 9.77 (1 H, br s), 8.36 (1 H, br s), 8.18 (1 H, d, J=8.6 Hz), 7.87-7.83 (2 H, m), 7.71-7.57 (3 H, m), 7.40 (1 H, dd, J=1.0, 7.6 Hz), 7.10 (1 H, dd, J=7.6, 8.4 Hz), 2.26 (3 H, s).

Workup

  1. stirringstirred for an additional 2 h
  2. customThe mixture was quenched with saturated aqueous ammonium chloride (20 ml)
  3. extractionextracted with ether (150 ml)
  4. washThe organic layer was washed with water (50 ml)
  5. dry with materialdried (MgSO4)
  6. customRemoval of solvent
  7. customgave an oily residue
  8. customPurification by flash column chromatography
  9. washeluting with ethyl acetate/hexane (1:3)
  10. customafforded yellow crystals
  11. customRecrystallization from ethyl acetate

Sources & evidence

ORD record
ord-c77dfd1a9073485ebb81502e80cee11c
Source dataset
uspto-grants-2001_10
Patent number
US06300363B1

Reaction notes

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