Potassium Carbonate → HCID 57972811, compound

HRID 661444Notes

Reaction equation

HRID 661444 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]([F:11])([F:10])[F:9])=[CH:4][CH:3]=1.[NH2:12][C@H:13]([CH2:18][CH3:19])[CH2:14][C:15]([OH:17])=[O:16].C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O.[Cu](I)I>[F:9][C:8]([F:11])([F:10])[C:5]1[CH:6]=[CH:7][C:2]([NH:12][C@H:13]([CH2:18][CH3:19])[CH2:14][C:15]([OH:17])=[O:16])=[CH:3][CH:4]=1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 67872Benzene, 1-bromo-4-(trifluoromethyl)-HCID 14731979(3R)-3-Aminopentanoic acid

Product 1

HCID 57972811HCID 57972811, compound

Reagents, catalysts & solvents 2

HCID 83717Copper iodideCatalystHCID 6228DimethylformamideSolvent

Procedure

To a solution of 1-bromo-4-trifluoromethylbenzene (2530 g, 11.24 mole) and (R)-3-aminovaleric acid (659 g, 5.63 mole) in N,N-dimethylformamide (12 liter), were added copper iodide (210 g, 1.10 mole) and potassium carbonate (2330 g, 16.86 mole), and the mixture was sealed under nitrogen atmosphere and stirred at 100° C.-120° C. for about 60 hours. When the reaction was completed, the reaction mixture was concentrated in vacuo at 60° C.-70° C. of the bath temperature, the residue was dissolved in water (6.0 liter) and the solution was adjusted to pH about 5.0 with addition of hydrochloric acid. Ethyl acetate (6.0 liter) was added and the mixture was stirred, filtered and washed with ethyl acetate (2.4 liter). The filtrate was separated and the aqueous layer was extracted with ethyl acetate (3.6 liter). The organic layer was combined and extracted with 25% ammonia water (3.0 liter) and water (3 liter). The aqueous layer was acidified to pH about 5.0 with addition of hydrochloric acid, and extracted with ethyl acetate (6.0 liter). The organic layer was dried over magnesium sulfate (600 g), filtered and washed with ethyl acetate (2.4 liter). The filtrate was concentrated in vacuo at 45° C.-55° C. of the bath temperature, and the titled compound was obtained as an oily residue, which was used in the next step without further purification.

Workup

  1. customthe mixture was sealed under nitrogen atmosphere
  2. concentrationthe reaction mixture was concentrated in vacuo at 60° C.-70° C. of the bath temperature
  3. dissolutionthe residue was dissolved in water (6.0 liter)
  4. additionthe solution was adjusted to pH about 5.0 with addition of hydrochloric acid
  5. additionEthyl acetate (6.0 liter) was added
  6. stirringthe mixture was stirred
  7. filtrationfiltered
  8. washwashed with ethyl acetate (2.4 liter)
  9. customThe filtrate was separated
  10. extractionthe aqueous layer was extracted with ethyl acetate (3.6 liter)
  11. extractionextracted with 25% ammonia water (3.0 liter) and water (3 liter)
  12. additionThe aqueous layer was acidified to pH about 5.0 with addition of hydrochloric acid
  13. extractionextracted with ethyl acetate (6.0 liter)
  14. dry with materialThe organic layer was dried over magnesium sulfate (600 g)
  15. filtrationfiltered
  16. washwashed with ethyl acetate (2.4 liter)
  17. concentrationThe filtrate was concentrated in vacuo at 45° C.-55° C. of the bath temperature

Sources & evidence

ORD record
ord-90e1941bb9694e3faae499bd26aebd06
Source dataset
uspto-grants-2011_12
Patent number
US08084611B2

Reaction notes

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