1-Bromopropane → HCID 11525777, compound

HRID 851954Notes

Reaction equation

HRID 851954 reaction equation
[OH:1][C:2]1[CH:7]=[CH:6][C:5]([C@@H:8]2[N:13]3[CH2:14][CH2:15][N:16]([C:18]([C:20]4[CH:21]=[N:22][C:23]([C:26]([F:29])([F:28])[F:27])=[CH:24][CH:25]=4)=[O:19])[CH2:17][C@@H:12]3[CH2:11][CH2:10][CH2:9]2)=[C:4]([CH3:30])[C:3]=1[CH3:31].[OH-].[K+].Br[CH2:35][CH2:36][CH3:37]>CC#N>[CH3:30][C:4]1[C:3]([CH3:31])=[C:2]([O:1][CH2:35][CH2:36][CH3:37])[CH:7]=[CH:6][C:5]=1[C@@H:8]1[N:13]2[CH2:14][CH2:15][N:16]([C:18]([C:20]3[CH:21]=[N:22][C:23]([C:26]([F:29])([F:28])[F:27])=[CH:24][CH:25]=3)=[O:19])[CH2:17][C@@H:12]2[CH2:11][CH2:10][CH2:9]1

Participants

5

Reactant 3

HCID 78401-BromopropaneHCID 14797Potassium HydroxideHCID 58928334HCID 58928334, compound

Product 1

HCID 11525777HCID 11525777, compound

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
60 °C

Procedure

A solution of [(6R,9aS)-6-(4-hydroxy-2,3-dimethylphenyl)-octahydro-pyrido[1,2-a]pyrazin-2-yl]-(6-trifluoromethyl-pyridin-3-yl)-methanone (1.54 g, 3.55 mmol) in CH3CN is treated with powdered KOH (400 mg, 7.10 mmol, 1.5 eq) and 1-bromopropane (5.33 mmol, 2.0 eq) and heated in a sealed tube reactor with stirring in a 60° C. oil bath for 20.5 h. After cooling, the mixture is filtered through a CELITE pad. The pad is washed with CH2Cl2 and the solution is concentrated in vacuo. The residue is purified by flash chromatography on silica gel eluting with 50%-40% hexanes/EtOAc to yield {(6R,9aS)-6-(2,3-dimethyl-4-propoxyphenyl)-hexahydro-1H-pyrido[1,2-a]pyrazin-2(6H)-yl}-(6-(trifluoromethyl)pyridin-3-yl)methanone. LC/MS: 476 (M+1).

Workup

  1. temperatureheated in a sealed tube reactor
  2. temperatureAfter cooling
  3. filtrationthe mixture is filtered through a CELITE pad
  4. washThe pad is washed with CH2Cl2
  5. concentrationthe solution is concentrated in vacuo
  6. customThe residue is purified by flash chromatography on silica gel eluting with 50%-40% hexanes/EtOAc

Sources & evidence

ORD record
ord-b6d3dbef449c4f94afae8ba32cb9b970
Source dataset
uspto-grants-2007_08
Patent number
US07253168B2

Reaction notes

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