Iodoethane → 3-Ethylindol-2-one

HRID 1370304Notes

Reaction equation

HRID 1370304 reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH2:3][C:2]1=[O:10].[CH2:11]([Li])[CH2:12]CC.CN(C)CCN(C)C.ICC.[NH4+].[Cl-]>C1COCC1>[CH2:11]([C:3]1[C:2](=[O:10])[N:1]=[C:9]2[C:4]=1[CH:5]=[CH:6][CH:7]=[CH:8]2)[CH3:12]

Participants

7

Reactant 5

HCID 6340IodoethaneHCID 8037N,N,N',N'-TetramethylethylenediamineHCID 25517Ammonium ChlorideHCID 321710OxindoleHCID 178418339Butyllithium

Product 1

HCID 219862793-Ethylindol-2-oneYield 2.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of oxindole (40 g, 0.3 mol) in dry THF (400 ml) under N2 was cooled to −25° C. and treated drop wise with n-butyl lithium (2.5M in hexanes, 240 ml, 0.6 mol). To the resulting solution was added N,N,N′,N′-tetramethylethylenediamine (90.4 ml, 0.6 mol). After 30 min. iodoethane (48 ml, 0.6 mol) was added and the reaction mixture was allowed to warm to room temperature and stirred over night. The reaction mixture was poured into aqueous NH4Cl 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 crude product (24.5 g, 51%). A sample (3 g) was recrystallized from EtOAc/hexane to obtain 3-ethyl-indol-2-one (1.4 g), m.p. 100-101° C.; 1H-NMR (DMSO-d6) δ 0.76 (t, 3H, J=7.5 Hz), 1.8-2.0 (m, 2H), 3.38 (t, 3H, J=5.7 Hz), 6.8 (dt, 1H, J=7.69, 0.45 Hz), 6.93 (dt, 1H, J=7.45, 1.10 Hz), 7.15 (m, 1H), 7.22 (m, 1H), 10.3 (s, 1H); MS (ESI) m/z 270 [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
  6. customto afford the crude product (24.5 g, 51%)
  7. customA sample (3 g) was recrystallized from EtOAc/hexane

Sources & evidence

ORD record
ord-d8e8032403fc43d3a617b16bb1fbb038
Source dataset
uspto-grants-2003_06
Patent number
US06583145B1

Reaction notes

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