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

HRID 444736Notes

Reaction equation

HRID 444736 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 (2.5 M 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 hours saturated aqueous ammonium chloride solution (1 L) and EtOAc (1 L) were added. After 15 minutes, the layers were separated and the aqueous phase was extracted using EtOAc (×2). The combined organic layers were extracted with hydrochloric acid (1 N), 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. waitAfter 15 minutes
  3. customthe layers were separated
  4. extractionthe aqueous phase was extracted
  5. extractionThe combined organic layers were extracted with hydrochloric acid (1 N)
  6. washwashed with brine (500 mL)
  7. dry with materialdried (MgSO4)
  8. concentrationconcentrated
  9. customto obtain an oil
  10. customThe oil was triturated with hexane (200 mL) and benzene (20 mL)
  11. customThe precipitate was collected
  12. customdried in vacuo

Sources & evidence

ORD record
ord-11ee778d35194ca78b1c14a6bac0c2de
Source dataset
uspto-grants-2013_07
Patent number
US08476262B2

Reaction notes

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