Triethylamine → HCID 74931357, compound

HRID 1095085Notes

Reaction equation

HRID 1095085 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]2[NH:8][C:9](=[O:38])[C:10]3([CH:15]([C:16]4[CH:21]=[CH:20][CH:19]=[C:18]([Cl:22])[CH:17]=4)[CH2:14][C:13](=[O:23])[NH:12][CH:11]3[C:24]3[CH:29]=[C:28]([I:30])[CH:27]=[CH:26][C:25]=3[O:31][CH:32]3[CH2:37][CH2:36][NH:35][CH2:34][CH2:33]3)[C:5]2=[CH:4][CH:3]=1.C(N(CC)CC)C.Br[CH2:47][CH2:48][OH:49]>C(O)C>[Cl:1][C:2]1[CH:7]=[C:6]2[NH:8][C:9](=[O:38])[C:10]3([CH:15]([C:16]4[CH:21]=[CH:20][CH:19]=[C:18]([Cl:22])[CH:17]=4)[CH2:14][C:13](=[O:23])[NH:12][CH:11]3[C:24]3[CH:29]=[C:28]([I:30])[CH:27]=[CH:26][C:25]=3[O:31][CH:32]3[CH2:33][CH2:34][N:35]([CH2:47][CH2:48][OH:49])[CH2:36][CH2:37]3)[C:5]2=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 108982-BromoethanolHCID 77156971HCID 77156971, compound

Product 1

HCID 74931357HCID 74931357, compoundYield 34%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of racemic(2′R, 3R, 4′S)-6-chloro-4′-(3-chlorophenyl)-2′-[5-iodo-2-(4-piperidinyloxy)-phenyl]spiro[3H-indole-3,3′-piperidine]-2,6′(1H)-dione (0.1 g, 0.15 mmol) prepared in example 5a in ethanol (2 mL) was added triethylamine (45.7 mg, 0.46 mmol) and 2-bromoethanol (42.4 mg, 0.345 mmol) (Aldrich). The reaction mixture was heated at 80° C. for 18 h, then cooled to room temperature and concentrated. The residue was partitioned between ethyl acetate and water. The organic layer was separated, and the aqueous layer was extracted with ethyl acetate. The organic layers were combined, washed with brine, dried over MgSO4, and concentrated. The residue was purified by chromatography (MeOH:EtOAc:NEt3=12:88:5) to give racemic(2′R, 3R, 4′S)-6-chloro-4′-(3-chlorophenyl)-2′-{2-[1-(2-hydroxy-ethyl)-4-piperidinyloxy]-5-iodo-phenyl}spiro[3H-indole-3,3′-piperidine]-2,6′(1H)-dione as a white solid (Yield 36 mg, 34%)

Workup

  1. temperaturecooled to room temperature
  2. concentrationconcentrated
  3. customThe residue was partitioned between ethyl acetate and water
  4. customThe organic layer was separated
  5. extractionthe aqueous layer was extracted with ethyl acetate
  6. washwashed with brine
  7. dry with materialdried over MgSO4
  8. concentrationconcentrated
  9. customThe residue was purified by chromatography (MeOH:EtOAc:NEt3=12:88:5)

Sources & evidence

ORD record
ord-dde43de2ec56444aa3d885ff5d06e922
Source dataset
uspto-grants-2012_03
Patent number
US08134001B2

Reaction notes

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