Formic Acid → 4-Formyl-1-trifluoroacetyl-1,4,5,6-tetrahydropyrazine-2-carboxylic acid tert-butylamide

HRID 1419515Notes

Reaction equation

HRID 1419515 reaction equation
S(Cl)(Cl)=O.[C:5]([NH:9][C:10]([C:12]1[N:13]([C:18](=[O:23])[C:19]([F:22])([F:21])[F:20])[CH2:14][CH2:15][NH:16][CH:17]=1)=[O:11])([CH3:8])([CH3:7])[CH3:6].[CH:24](O)=[O:25]>>[C:5]([NH:9][C:10]([C:12]1[N:13]([C:18](=[O:23])[C:19]([F:22])([F:20])[F:21])[CH2:14][CH2:15][N:16]([CH:24]=[O:25])[CH:17]=1)=[O:11])([CH3:8])([CH3:6])[CH3:7]

Participants

4

Reactant 3

HCID 284Formic AcidHCID 24386Thionyl ChlorideHCID 117479071-Trifluoroacetyl-1,4,5,6-tetra-hydropyrazine-2-carboxylic acid tert-butylamide

Product 1

HCID 540332824-Formyl-1-trifluoroacetyl-1,4,5,6-tetrahydropyrazine-2-carboxylic acid tert-butylamide

Procedure

49.60 g (416.9 mmol) of thionyl chloride was added over 40 min at 20° C. to a solution of 96.94 g (347.1 mmol) of 1-trifluoroacetyl-1,4,5,6-tetrahydropyrazine-2-carboxylic acid tert-butylamide in 465.9 g (10.1 mol) of formic acid. After a reaction time of 2 hours at 20° C., the mixture was concentrated on a rotary evaporator at 60° C. and 80 mbar and the brownish-black residue was taken up with 400 ml of ethyl acetate and 400 ml of water. The aqueous phase was washed again with twice 250 ml of ethyl acetate and the combined organic extracts were dried over 50.1 g of sodium sulfate. After filtration, the solution was concentrated on a rotary evaporator and the viscous residue was stirred with 250 ml of diisopropyl ether. The precipitated solid was filtered off, washed with twice 100 ml of diisopropyl ether and dried. The yield was 96.76 g (91 %) of colorless crystals. The melting point of the title compound was: 158.4° to 160.3° C. Other data concerning the title compound was:

Workup

  1. concentrationAfter a reaction time of 2 hours at 20° C., the mixture was concentrated on a rotary evaporator at 60° C.
  2. washThe aqueous phase was washed again with twice 250 ml of ethyl acetate
  3. dry with materialthe combined organic extracts were dried over 50.1 g of sodium sulfate
  4. filtrationAfter filtration
  5. concentrationthe solution was concentrated on a rotary evaporator
  6. filtrationThe precipitated solid was filtered off
  7. washwashed with twice 100 ml of diisopropyl ether
  8. customdried
  9. custom158.4° to 160.3° C

Sources & evidence

ORD record
ord-f37a5949b3414f008098e34fb758d3f8
Source dataset
uspto-grants-1999_03
Patent number
US05886181

Reaction notes

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