Hydrochloric Acid → 1-(2-Amino-5-chlorophenyl)-2,2,2-trifluoroethan-1-one--hydrogen chloride--water (1/1/1)

HRID 582908Notes

Reaction equation

HRID 582908 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8]C(=[O:14])C(C)(C)C)=[CH:4][CH:3]=1.CN(CCN(C)C)C.C([Li])CCC.CCCCCC.[F:34][C:35]([F:42])([F:41])[C:36](OCC)=[O:37].Cl>COC(C)(C)C>[OH2:14].[ClH:1].[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([NH2:8])=[C:6]([C:36](=[O:37])[C:35]([F:42])([F:41])[F:34])[CH:7]=1

Participants

8

Reactant 6

HCID 313Hydrochloric Acid2×HCID 8037N,N,N',N'-TetramethylethylenediamineHCID 8058HexaneHCID 9794Ethyl trifluoroacetateHCID 182511Propanamide, N-(4-chlorophenyl)-2,2-dimethyl-HCID 178418339Butyllithium

Product 1

HCID 441819891-(2-Amino-5-chlorophenyl)-2,2,2-trifluoroethan-1-one--hydrogen chloride--water (1/1/1)Yield 175%

Reagents, catalysts & solvents 1

HCID 15413tert-Butyl methyl etherSolvent

Conditions

Temperature
-20 °C

Procedure

N-(4-Chlorophenyl)-2,2-dimethyl propanamide (36.7 kg, 173 mol) was charged to a solution of TMEDA (20.2 kg, 174 mol) in anhydrous t-butyl methyl ether (271.5 kg) and cooled to -20° C. To the cold slurry was added 2.7 N n-butyllithium in hexane (101.9 kg, 393 mol) while keeping the temperature below 5° C. After aging 2 hr at 0 to 5° C., the solution was cooled below -15° C. then rapidly reacted with ethyl trifluoroacetate (34.5 kg, 243 mol). After 30 min, the resulting solution was quenched into 3N HCl (196 L, 589 mol) keeping the temperature below 25° C. After removal of the aqueous phase, the organic solution was concentrated by distilling approximately 200 L of solvent. Acetic acid (352 kg) was added while distilling 325 kg solvent under 100 mm vacuum. After cooling the solution to 30° C., 12 N HCl (43.4 kg, 434 mol) was added and the mixture heated to 65 to 70° C. and held 4 hours. The resulting slurry was cooled to 5° C. and the product was collected by filtration, washed with ethyl acetate (50.5 kg) and dried in vacuo to give 42.1 kg (87%) of the title compound as a white crystalline solid: mp 159-162 dec; 1H NMR (300 MHz, DMSO-d6) d 7.65-7.5 (complex, 2H), 7.1 (d, J=8 Hz, 1H), 7.0 (brs, 3H); 19F NMR (282 MHz, DMSO-d6) δ -69.5.

Workup

  1. customthe temperature below 5° C
  2. temperaturethe solution was cooled below -15° C.
  3. waitAfter 30 min
  4. customthe temperature below 25° C
  5. customAfter removal of the aqueous phase
  6. concentrationthe organic solution was concentrated
  7. distillationby distilling approximately 200 L of solvent
  8. additionAcetic acid (352 kg) was added
  9. distillationwhile distilling 325 kg solvent under 100 mm vacuum
  10. temperatureAfter cooling the solution to 30° C.
  11. temperaturethe mixture heated to 65 to 70° C.
  12. waitheld 4 hours
  13. temperatureThe resulting slurry was cooled to 5° C.
  14. filtrationthe product was collected by filtration
  15. washwashed with ethyl acetate (50.5 kg)
  16. customdried in vacuo

Sources & evidence

ORD record
ord-4da56557808d408fa0e122208147da01
Source dataset
uspto-grants-1999_07
Patent number
US05925789

Reaction notes

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