Sodium Hydroxide → 5-Bromospiro[indoline-3,4'-piperidin]-2-one

HRID 661343Notes

Reaction equation

HRID 661343 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]2[C:10]3([CH2:15][CH2:14][N:13](C#N)[CH2:12][CH2:11]3)[C:9](=[O:18])[NH:8][C:5]2=[CH:6][CH:7]=1.[OH-].[Na+]>C(O)CO.C(Cl)Cl>[Br:1][C:2]1[CH:3]=[C:4]2[C:10]3([CH2:11][CH2:12][NH:13][CH2:14][CH2:15]3)[C:9](=[O:18])[NH:8][C:5]2=[CH:6][CH:7]=1

Participants

5

Reactant 2

HCID 14798Sodium HydroxideHCID 596575285-bromo-1'-(cyano)spiro[indole-3,4'-piperidin]-2(1H)-one

Product 1

HCID 596575825-Bromospiro[indoline-3,4'-piperidin]-2-oneYield 60%

Reagents, catalysts & solvents 2

HCID 174Ethylene GlycolSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
130 °C

Procedure

5-Bromo-1,2-dihydro-2-oxospiro[3H-indole-3,4′-piperidine]-1′-cyano 12 (3.3 g, 10.8 mmol) was suspended in ethylene glycol (10 ml). The mixture was treated in NaOH (1.8 g, 45 mmol) and heated to 130° C. for 15 min. It was diluted with methylene chloride (500 ml) and washed with 10% aqueous K2CO3 (2×100 m). The organic layer was dried (Na2SO4) and concentrated and residue purified by silica gel chromatography (30% MeOH/CH2Cl2) to gave 13 as a light ceramic white solid 1.8 g (60%), mp 256-258° C. 1HNMR (DMSO-d6, 400 MHz) δ 10.6 (br s, 1H, NH), 7.57 (d, J=1.84 Hz, 1H), 7.36 (d, J=8.2 Hz, 1H), 6.79 (d, J=8.2 Hz, 1H), 4.05 (br s, 1H, NH), 3.06 (m, 2H), 2.84 (m, 2H), 1.64 (m, 2H), 1.55 (m, 2H), 13C NMR (DMSO-d6, 100 MHz) δ 180.93, 140.64, 137.98, 130.42, 126.75, 113.20, 111.45, 46.24, 40.92, 32.94. Anal. Calcd for C12H13BrN2O: C, 51.26; H, 4.66; N, 9.9. Found: C, 50.87; H, 4.91; N, 9.67.

Workup

  1. washwashed with 10% aqueous K2CO3 (2×100 m)
  2. dry with materialThe organic layer was dried (Na2SO4)
  3. concentrationconcentrated
  4. customresidue purified by silica gel chromatography (30% MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-4e714e4d6e004831a5b1bff46d0bd374
Source dataset
uspto-grants-2011_12
Patent number
US08084609B2

Reaction notes

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