Sodium Bicarbonate → Methyl 4-cyclopentyl-3-(trifluoromethyl)benzoate

HRID 2274088Notes

Reaction equation

HRID 2274088 reaction equation
Cl[C:2]1[CH:10]=[CH:9][C:5]([C:6]([O-:8])=[O:7])=[CH:4][C:3]=1[C:11]([F:14])([F:13])[F:12].[Br-].[CH:16]1([Zn+])[CH2:20][CH2:19][CH2:18][CH2:17]1.[C:22]([O-])(O)=O.[Na+]>C1COCC1.CC(C)([P](C(C)(C)C)([Pd][P](C(C)(C)C)(C(C)(C)C)C(C)(C)C)C(C)(C)C)C>[CH:16]1([C:2]2[CH:10]=[CH:9][C:5]([C:6]([O:8][CH3:22])=[O:7])=[CH:4][C:3]=2[C:11]([F:14])([F:13])[F:12])[CH2:20][CH2:19][CH2:18][CH2:17]1

Participants

6

Reactant 3

HCID 516892Sodium BicarbonateHCID 70093564-Chloro-3-(trifluoromethyl)benzoateHCID 178419768HCID 178419768, compound

Product 1

HCID 11097668Methyl 4-cyclopentyl-3-(trifluoromethyl)benzoate

Reagents, catalysts & solvents 2

HCID 178418851HCID 178418851, compoundCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
70 °C

Procedure

To a solution of 4-chloro-3-(trifluoromethyl)benzoate (196.7 g, 824 mmol) in THF (100 mL), cyclopentylzinc(II) bromide (1979 mL, 989 mmol) was added dropwise at 7.8° C. The temperature at the end of the addition rose to 22° C. bis(Tri-t-butylphosphine)palladium (21.07 g, 41.2 mmol) was added to the dark brown solution at the same temperature, and the resulting mixture was stirred at 70° C. for 8 h. The mixture was added to saturated aqueous NaHCO3 (100 mL) at 0° C., stirred at the same temperature for 30 min and then at 22° C. for 2 h. The resulting suspension was filtered through Celite and the filtrate concentrated under vacuum. The solids were washed with EtOAc (3×300 mL), the filtrate was combined with the previous concentrate and the combined organics were washed with H2O (2×600 mL), brine (2×500 mL), dried (Na2SO4), decanted and concentrated under reduced pressure to give the title compound as an orange oil (227 g) without further purification. LCMS m/z=273.4 [M+H]+; NMR (400 MHz, CDCl3) δ ppm 1.71-1.60 (m, 2H), 1.83-1.75 (m, 2H), 1.95-1.87 (m, 2H), 2.21-2.11 (m, 2H), 3.46 (quintet, J=8.8 Hz, 1H), 3.97 (s, 3H), 7.58 (d, J=8.4 Hz, 1H), 8.18 (dd, J=8.0 Hz, 1.6 Hz, 1H), 8.31 (d, J=1.6 Hz, 1H).

Workup

  1. additionThe temperature at the end of the addition
  2. customrose to 22° C.
  3. additionwas added to the dark brown solution at the same temperature
  4. stirringstirred at the same temperature for 30 min
  5. waitat 22° C. for 2 h
  6. filtrationThe resulting suspension was filtered through Celite
  7. concentrationthe filtrate concentrated under vacuum
  8. washThe solids were washed with EtOAc (3×300 mL)
  9. concentrationprevious concentrate
  10. washthe combined organics were washed with H2O (2×600 mL), brine (2×500 mL)
  11. dry with materialdried (Na2SO4)
  12. customdecanted
  13. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-d455a6eedd5b47bea533750e91bccf5a
Source dataset
uspto-grants-2015_09
Patent number
US09126932B2

Reaction notes

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