Hydrochloric Acid → 5-(3-Chloro-phenyl)-3,3-diethyl-1,3-dihydro-indol-2-one

HRID 990643Notes

Reaction equation

HRID 990643 reaction equation
[CH2:1]([C:3]1[C:4](=[O:12])[N:5]=[C:6]2[C:11]=1[CH:10]=[CH:9][CH:8]=[CH:7]2)[CH3:2].[CH2:13]([Li])[CH2:14][CH2:15][CH3:16].CN(C)[CH2:20][CH2:21]N(C)C.I[CH2:27][CH3:28].[ClH:29]>C1COCC1>[Cl:29][C:14]1[CH:15]=[C:16]([C:9]2[CH:10]=[C:11]3[C:6](=[CH:7][CH:8]=2)[NH:5][C:4](=[O:12])[C:3]3([CH2:20][CH3:21])[CH2:1][CH3:2])[CH:27]=[CH:28][CH:13]=1

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 6340IodoethaneHCID 8037N,N,N',N'-TetramethylethylenediamineHCID 219862793-Ethylindol-2-oneHCID 178418339Butyllithium

Product 1

HCID 99482465-(3-Chloro-phenyl)-3,3-diethyl-1,3-dihydro-indol-2-oneYield 45%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of 3-ethylindol-2-one (16 g, 0.1 mol) in dry THF (200 ml) under N2 was cooled to −25° C. and treated drop wise with n-butyllithium (2.5M in hexanes, 80 ml, 0.2 mol). To the resulting solution was added N,N,N′,N′-tetramethylethylenediamine (30 ml, 0.2 mol). After 30 min. iodoethane (8 ml, 0.1 mol) was added and the reaction rnixture was allowed to warm to RT and stirred over night. The reaction mixture was poured into an aqueous HCl solution, extracted with EtOAc (2×) and the combined organic layers were washed with dil. HCl, water, brine, dried (MgSO4) and concentrated. The residual oil was triturated with hexane to afford the title product (9 g, 45%), mp. 156-159° C. 1H NMR (DMSO-d6) δ 10.44 (s, 1H), 7.70-7.69 (t, 1H), 7.62-7.59 (m, 1H), 7.58 (d, 1H J=1.7 Hz), 7.53-7.50 (m, 1H), 7.45-7.41 (t, 1H), 7.36-7.35 (m, 1H), 7.34-7.33 (m, 1H), 6.91-6.89 (d, 1H J=8.2 Hz), 1.87-1.80 (m, 2H), 1.77-1.70 (m, 2H), 0.54-0.50 (t, 6H); MS (+ESI) m/z 190 (M+H).

Workup

  1. extractionextracted with EtOAc (2×)
  2. washthe combined organic layers were washed with dil. HCl, water, brine
  3. dry with materialdried (MgSO4)
  4. concentrationconcentrated
  5. customThe residual oil was triturated with hexane

Sources & evidence

ORD record
ord-a0dc37b3a01e44b29e9052bcbabeb776
Source dataset
uspto-grants-2002_10
Patent number
US06462032B1

Reaction notes

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