Hydrochloric Acid → HCID 57972811, compound

HRID 661446Notes

Reaction equation

HRID 661446 reaction equation
[NH2:1][C@H:2]([CH2:7][CH3:8])[CH2:3][C:4]([OH:6])=[O:5].Br[C:10]1[CH:15]=[CH:14][C:13]([C:16]([F:19])([F:18])[F:17])=[CH:12][CH:11]=1.C(=O)([O-])[O-].[K+].[K+].Cl>[Cu](I)I.C1(C)C=CC=CC=1.O.CS(C)=O>[F:17][C:16]([F:19])([F:18])[C:13]1[CH:14]=[CH:15][C:10]([NH:1][C@H:2]([CH2:7][CH3:8])[CH2:3][C:4]([OH:6])=[O:5])=[CH:11][CH:12]=1

Participants

9

Reactant 4

HCID 313Hydrochloric AcidHCID 11430Potassium CarbonateHCID 67872Benzene, 1-bromo-4-(trifluoromethyl)-HCID 14731979(3R)-3-Aminopentanoic acid

Product 1

HCID 57972811HCID 57972811, compound

Reagents, catalysts & solvents 4

HCID 83717Copper iodideCatalystHCID 679Dimethyl SulfoxideSolventHCID 962WaterSolventHCID 1140TolueneSolvent

Conditions

Temperature
110 °C

Procedure

(R)-3-Aminovaleric acid (12 kg), 1-bromo-4-trifluoromethylbenzene (34.6 kg), copper iodide (3.9 kg) and potassium carbonate (28.3 kg) were added to dimethylsulfoxide (120 liter), and the mixture was sealed under nitrogen atmosphere and stirred at 100-120° C. for 48 hours. After the reaction mixture was cooled, water (120 liter) and toluene (120 liter) were added, the value of the pH was adjusted to below 3 with addition of hydrochloric acid and the solution was separated. The aqueous layer was extracted with toluene (120 liter) and the combined organic layer was washed with water (120 liter). 25% ammonia water (60 liter) and water (60 liter) were added to the organic layer and extracted. The aqueous layer was adjusted to pH 3-4 with addition of hydrochloric acid and extracted with toluene (120 liter). The filtrate was concentrated in vacuo at 30-70° C. of the bath temperature, n-heptane (24 liter) was added to the residue and concentrated twice to give the titled compound as an oily residue. The product was used in the next step without further purification. MS (APCI) m/z: 262 [M+H]+.

Workup

  1. customthe mixture was sealed under nitrogen atmosphere
  2. temperatureAfter the reaction mixture was cooled
  3. customthe solution was separated
  4. extractionThe aqueous layer was extracted with toluene (120 liter)
  5. washthe combined organic layer was washed with water (120 liter)
  6. addition25% ammonia water (60 liter) and water (60 liter) were added to the organic layer
  7. extractionextracted
  8. additionThe aqueous layer was adjusted to pH 3-4 with addition of hydrochloric acid
  9. extractionextracted with toluene (120 liter)
  10. concentrationThe filtrate was concentrated in vacuo at 30-70° C. of the bath temperature, n-heptane (24 liter)
  11. additionwas added to the residue
  12. concentrationconcentrated twice

Sources & evidence

ORD record
ord-c18d51e9ff134c97a19c0956044e4440
Source dataset
uspto-grants-2011_12
Patent number
US08084611B2

Reaction notes

Loading…