Methyl Acrylate → (2R)-4-[5-(2-Methoxycarbonyl-vinyl)-3-trifluoromethyl-pyridin-2-yl]-2-methyl-piperazine-1-carboxylic acid tert-butyl ester

HRID 730904Notes

Reaction equation

HRID 730904 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[C:19]([C:20]([F:23])([F:22])[F:21])=[CH:18][C:17](Br)=[CH:16][N:15]=2)[CH2:10][C@H:9]1[CH3:25])=[O:7])([CH3:4])([CH3:3])[CH3:2].[C:26]([O:30][CH3:31])(=[O:29])[CH:27]=[CH2:28]>[Cl-].C([N+](CC)(CC)CC)C1C=CC=CC=1.CN(C=O)C.O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[C:19]([C:20]([F:23])([F:22])[F:21])=[CH:18][C:17]([CH:28]=[CH:27][C:26]([O:30][CH3:31])=[O:29])=[CH:16][N:15]=2)[CH2:10][C@H:9]1[CH3:25])=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 2

HCID 7294Methyl AcrylateHCID 11575439(2R)-4-(5-Bromo-3-trifluoromethyl-pyridin-2-yl)-2-methyl-piperazine-1-carboxylic acid tert-butyl ester

Product 1

HCID 67400642(2R)-4-[5-(2-Methoxycarbonyl-vinyl)-3-trifluoromethyl-pyridin-2-yl]-2-methyl-piperazine-1-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 4

HCID 66133Benzyl triethylammonium chlorideCatalystHCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
40 °C

Procedure

A mixture of (2R)-4-(5-bromo-3-trifluoromethyl-pyridin-2-yl)-2-methyl-piperazine-1-carboxylic acid tert-butyl ester from step (c) above (8.48 g, 20 mmol), methyl acrylate (1.9 g, 22 mmol, Aldrich), palladium acetate (49 mg, 2.0 mmol, Aldrich) and benzyltriethyl ammonium chloride (456 mg, 2.0 mmol, Aldrich) in DMF (20 mL) was stirred at 40° C. for 18 h. The reaction mixture was cooled to room temperature, diluted with water (50 mL) and extracted with EtOAc (2×80 mL). The combined organic extracts were washed with brine (40 mL), dried over Na2SO4 and filtered. The filtrate was evaporated in vacuo and the residue was purified by silica gel column chromatography, eluting with 20% EtOAc/hexane to give the title compound as a white solid. MS (ESI, pos. ion) m/e: 430 (M+1).

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. extractionextracted with EtOAc (2×80 mL)
  3. washThe combined organic extracts were washed with brine (40 mL)
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. customThe filtrate was evaporated in vacuo
  7. customthe residue was purified by silica gel column chromatography
  8. washeluting with 20% EtOAc/hexane

Sources & evidence

ORD record
ord-71a634763d724e0da5e35b4b73f663de
Source dataset
uspto-grants-2009_09
Patent number
US07582761B2

Reaction notes

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