N,N,N',N'-Tetramethylethylenediamine → 1',2'-Dihydrospiro[cyclopentane-1,3'-indole]-2'-one

HRID 6995

Reaction equation

HRID 6995 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][CH2:13][CH3:14].CN(C)CCN(C)C.ICCCCI>C1COCC1.O>[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]2([CH2:14][CH2:13][CH2:12][CH2:11]2)[C:2]1=[O:10]

Participants

7

Reactant 4

HCID 8037N,N,N',N'-TetramethylethylenediamineHCID 123371,4-DiiodobutaneHCID 321710OxindoleHCID 178418339Butyllithium

Product 1

HCID 3633431',2'-Dihydrospiro[cyclopentane-1,3'-indole]-2'-oneYield 50%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

To a −25° C. solution of oxindole (2.0 g, 15.0 mmol) in 40 (cm3) of anhydrous THF under N2 was added n-butyllithium (1.6 M in hexanes, 19.7 cm3, 31.5 mmol) drop-wise. To the resulting milky solution was added N,N,N′,N′-tetramethylethylenediamine (4.75 cm3, 31.5 mmol). After 30 min. a solution of 1,4-diiodobutane (21.9 g, 70.6 mmol) in THF (3 cm3) was added and the reaction mixture was allowed to warm to RT and stirred for 14 h. The reaction mixture was poured into water, extracted with EtOAc (×2), then the combined organic layers were washed with dil. HCl (pH 1), water (×2), dried (MgSO4) and evaporated. The residue was purified by column chromatography (SiO2, EtOAc: hexane 1:4) to afford the subtitled compound (1.4 g, 7.5 mmol, 50%) as a tan solid: 1H NMR (CDCl3) δ 1.8–2.2 (m, 8H), 6.94 (dd, J=7.5, 1.0 Hz, 1H), 7.01 (dd, J=7.5, 1.0 Hz, 1H), 7.14–7.25 (m, 2H), 9.30 (br s, 1H).

Workup

  1. extractionextracted with EtOAc (×2)
  2. washthe combined organic layers were washed with dil. HCl (pH 1), water (×2)
  3. dry with materialdried (MgSO4)
  4. customevaporated
  5. customThe residue was purified by column chromatography (SiO2, EtOAc: hexane 1:4)

Sources & evidence

ORD record
ord-0951505fdd3d4c26a4e8069af7835193
Source dataset
uspto-grants-2006_08
Patent number
US07084168B2

Linked notes

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