N,N,N',N'-Tetramethylethylenediamine → Spiro[cyclohexane-1,3'-indolin]-2'-one

HRID 6997

Reaction equation

HRID 6997 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].C([Li])CCC.CN(C)CCN(C)C.I[CH2:25][CH2:26][CH2:27][CH2:28][CH2:29]I.[Cl-].[NH4+]>O1CCCC1.CCOC(C)=O>[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]2([CH2:29][CH2:28][CH2:27][CH2:26][CH2:25]2)[C:2]1=[O:10]

Participants

8

Reactant 5

HCID 8037N,N,N',N'-TetramethylethylenediamineHCID 123541,5-DiiodopentaneHCID 25517Ammonium ChlorideHCID 321710OxindoleHCID 178418339Butyllithium

Product 1

HCID 12888301Spiro[cyclohexane-1,3'-indolin]-2'-oneYield 69.6%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of oxindole (25 g, 0.19 mol) in anhydrous tetrahydrofuran (800 cm3) was cooled to −20° C., then n-butyllithium (2.5M in hexanes, 152 cm3, 0.38 mol) was added slowly followed by N,N,N′,N′-tetramethylethylenediamine (51 cm3, 0.38 mol,). After 15 min. 1,5-diiodopentane (174 g, 0.54 mol) was added slowly and the mixture was allowed to warm to room temperature. After stirring for 16 h. saturated aqueous ammonium chloride solution (1 L) and EtOAc (1 L) were added. After 15 min. the layers were separated and the aqueous phase was extracted EtOAc (×2). The combined organic layers were extracted with hydrochloric acid (1N), then washed with brine (500 cm3), dried (MgSO4), and concentrated to obtain an oil. The oil was triturated with hexane (200 cm3) and benzene (20 cm3). The precipitate was collected and dried in vacuo to obtain the subtitled compound (26.3 g, 69.6%) as colorless crystals: mp 110–114° C.; 1H NMR (DMSO-d6) δ 1.67 (m, 10H), 6.84 (d, 1H, J=8 Hz) 6.94 (t, 1H, J=8 Hz), 7.17 (t, 1H, J=8 Hz), 7.44 (d, 1H, J=8 Hz), 10.3 (s, 1H).

Workup

  1. additionwere added
  2. customAfter 15 min. the layers were separated
  3. extractionthe aqueous phase was extracted EtOAc (×2)
  4. extractionThe combined organic layers were extracted with hydrochloric acid (1N)
  5. washwashed with brine (500 cm3)
  6. dry with materialdried (MgSO4)
  7. concentrationconcentrated
  8. customto obtain an oil
  9. customThe oil was triturated with hexane (200 cm3) and benzene (20 cm3)
  10. customThe precipitate was collected
  11. customdried in vacuo

Sources & evidence

ORD record
ord-d24153be9c474bb28c86121b580a0c0d
Source dataset
uspto-grants-2006_08
Patent number
US07084168B2

Linked notes

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