Triethylamine → HCID 15341179, compound

HRID 1440200Notes

Reaction equation

HRID 1440200 reaction equation
Cl[CH:2]([CH3:15])[C:3]([C:5]1[CH:6]=[C:7]2[C:11](=[CH:12][CH:13]=1)[NH:10][C:9](=[O:14])[CH2:8]2)=[O:4].[OH:16][C:17]1([CH2:23][C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[CH2:22][CH2:21][NH:20][CH2:19][CH2:18]1.C(N(CC)CC)C>C(O)C>[CH2:23]([C:17]1([OH:16])[CH2:22][CH2:21][N:20]([CH:2]([CH3:15])[C:3]([C:5]2[CH:6]=[C:7]3[C:11](=[CH:12][CH:13]=2)[NH:10][C:9](=[O:14])[CH2:8]3)=[O:4])[CH2:19][CH2:18]1)[C:24]1[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 981524-Benzyl-4-piperidinolHCID 14580231HCID 14580231, compound

Product 1

HCID 15341179HCID 15341179, compoundYield 84.9%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

5-(2-Chloropropionyl)-2(1H,3H)-indolone (2.5 g, 11.2 mmol), 4-hydroxy-4-benzylpiperadine (2.1 g, 11.2 mmol), and triethylamine (1.56 ml, 11.2 mmol) were combined in ethanol and refluxed overnight. The mixture was cooled to room temperature and concentrated at reduced pressure. The residue was partitioned between ethyl acetate and water and the phases were separated. The aqueous layer was extracted with ethyl acetate and the combined organic phase was washed with brine, dried over calcium sulfate, and concentrated. The crude product was flash chromatographed on silica gel eluting first unreacted 5-(2-chloropropionyl)-2(1H,3H)-indolone with 1:1 ethyl acetate:hexane. Continued elution with ethyl acetate gave 3.6 g of product as a light brown foam. Recrystallization from ethyl acetate/hexane gave 1.23 g of purified title product. Less pure fractions from the column and mother liquors from the recrystallization were rechromatographed as above with 1:1 and then 3:1 ethyl acetate:hexane. Product fractions were triturated with ether/hexane to give 0.2 g more product for a total yield of 1.43 g, 34%; m.p. 188°-192° C.; NMR 8.22 (s, 1H), 8.08 (d, J=8 Hz, 2H), 7.99 (s, 1H), 7.31-7.13 (m, 5H), 6.89 (d, J=8 Hz, 1H), 4.03 (q, J=6.8 Hz, 1H), 3.57 (s, 2H), 2.72 (s, 2H), 2.72-2.58 (m, 3H), 2.46 (distorted t, 1H), 1.75-1.40 m, 4H), 1.26 (d, J=6.8 Hz, 3H), 1.23-1.19 (m, 1H).

Workup

  1. temperaturerefluxed overnight
  2. concentrationconcentrated at reduced pressure
  3. customThe residue was partitioned between ethyl acetate and water
  4. customthe phases were separated
  5. extractionThe aqueous layer was extracted with ethyl acetate
  6. washthe combined organic phase was washed with brine
  7. dry with materialdried over calcium sulfate
  8. concentrationconcentrated
  9. customchromatographed on silica gel eluting first unreacted 5-(2-chloropropionyl)-2(1H,3H)-indolone with 1:1 ethyl acetate
  10. washContinued elution with ethyl acetate

Sources & evidence

ORD record
ord-c62256eee2c144e496d7d13454e7b8c4
Source dataset
uspto-grants-1996_03
Patent number
US05498610

Reaction notes

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