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

HRID 412391Notes

Reaction equation

HRID 412391 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 mL) was cooled to −20° C., then n-butyllithium (2.5M in hexanes, 152 mL, 0.38 mol) was added slowly followed by N,N,N′,N′-tetramethylethylenediamine (51 mL, 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 (1L) and EtOAc (1L) were added. After 15 min. the layers were separated and the aqueous phase was extracted using EtOAc (×2). The combined organic layers were extracted with hydrochloric acid (1N), then washed with brine (500 mL), dried (MgSO4), and concentrated to obtain an oil. The oil was triturated with hexane (200 mL) and benzene (20 mL). The precipitate was collected and dried in vacuo to obtain spiro[cyclohexane-1,3′-[3H]indol]-2′-(1′H)one (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
  4. extractionThe combined organic layers were extracted with hydrochloric acid (1N)
  5. washwashed with brine (500 mL)
  6. dry with materialdried (MgSO4)
  7. concentrationconcentrated
  8. customto obtain an oil
  9. customThe oil was triturated with hexane (200 mL) and benzene (20 mL)
  10. customThe precipitate was collected
  11. customdried in vacuo

Sources & evidence

ORD record
ord-f487340184874f96b9e0e16b256bd285
Source dataset
uspto-grants-2003_05
Patent number
US06562857B2

Reaction notes

Loading…