Hydrochloric Acid → (S)-1-(Trifluoroacetyl)piperazine-2-carboxylic acid tert-butylamide

HRID 1419520Notes

Reaction equation

HRID 1419520 reaction equation
Cl.O.[C:3]([NH:7][C:8]([C@@H:10]1[CH2:15][N:14](C=O)[CH2:13][CH2:12][N:11]1[C:18](=[O:23])[C:19]([F:22])([F:21])[F:20])=[O:9])([CH3:6])([CH3:5])[CH3:4].C(N(CC)CC)C>CC(C)=O>[C:3]([NH:7][C:8]([C@@H:10]1[CH2:15][NH:14][CH2:13][CH2:12][N:11]1[C:18](=[O:23])[C:19]([F:22])([F:20])[F:21])=[O:9])([CH3:6])([CH3:4])[CH3:5]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 962WaterHCID 8471TriethylamineHCID 53801860(S)-4-Formyl-1-(trifluoroacetyl)piperazine-2-carboxylic acid tert-butylamide

Product 1

HCID 54528768(S)-1-(Trifluoroacetyl)piperazine-2-carboxylic acid tert-butylamideYield 81.1%

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Conditions

Temperature
20 °C

Procedure

A mixture of 50.5 g (430 mmol) of 32% hydrochloric acid and 50 ml of water was added to 32.0 g (103 mmol) of (S)-4-formyl-1-(trifluoroacetyl) piperazine-2-carboxylic acid tert-butylamide in 200 ml of acetone and the resulting mixture was heated at 60° to 65° C. for 2.5 hours. After cooling to 20° C., neutralization was carried out with triethylamine in such a way that the temperature remained below 30° C. The solvent was evaporated off, and 100 ml of water and 200 ml of methyl isobutyl ketone were added. At 50° C. the phases were separated and the aqueous phase was re-extracted with twice 100 ml of methyl isobutyl ketone. The combined organic extracts were dried over magnesium sulfate and evaporated to dryness to give 23.5 g (80%) of the title compound in the form of a slightly reddish solid. Recrystallization from toluene/diisopropyl ether gave the title compound in the form of a white crystalline powder. The melting point of the title compound was: 143.5° to 144.2° C. Other data concerning the title compound was:

Workup

  1. temperaturethe resulting mixture was heated at 60° to 65° C. for 2.5 hours
  2. customremained below 30° C
  3. customThe solvent was evaporated off
  4. addition100 ml of water and 200 ml of methyl isobutyl ketone were added
  5. customAt 50° C. the phases were separated
  6. extractionthe aqueous phase was re-extracted with twice 100 ml of methyl isobutyl ketone
  7. dry with materialThe combined organic extracts were dried over magnesium sulfate
  8. customevaporated to dryness

Sources & evidence

ORD record
ord-118716679ac44807b8efd50ed0525fb6
Source dataset
uspto-grants-1999_03
Patent number
US05886181

Reaction notes

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