Hydrochloric Acid → 2-(4-Bromo-2-fluorobenzyl)-1,3-dioxo-1,2,3,4-tetrahydropyrrolo[1,2-a]pyrazine-4-carboxylic acid ethyl ester

HRID 256588Notes

Reaction equation

HRID 256588 reaction equation
C(O[C:4](=[O:22])[CH:5]([N:11]1[CH:15]=[CH:14][CH:13]=[C:12]1[C:16](=[O:21])C(Cl)(Cl)Cl)[C:6]([O:8][CH2:9][CH3:10])=[O:7])C.Cl.[Br:24][C:25]1[CH:32]=[CH:31][C:28]([CH2:29][NH2:30])=[C:27]([F:33])[CH:26]=1.C(N(CC)CC)C.Cl>CN(C)C=O>[CH2:9]([O:8][C:6]([CH:5]1[N:11]2[CH:15]=[CH:14][CH:13]=[C:12]2[C:16](=[O:21])[N:30]([CH2:29][C:28]2[CH:31]=[CH:32][C:25]([Br:24])=[CH:26][C:27]=2[F:33])[C:4]1=[O:22])=[O:7])[CH3:10]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 105471632-(2-Trichloroacetylpyrrol-1-yl)malonic acid diethyl esterHCID 184681974-Bromo-2-fluorobenzylamine hydrochloride

Product 1

HCID 106214602-(4-Bromo-2-fluorobenzyl)-1,3-dioxo-1,2,3,4-tetrahydropyrrolo[1,2-a]pyrazine-4-carboxylic acid ethyl esterYield 86%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
70 °C

Procedure

A mixture of 2-(2-trichloroacetylpyrrol-1-yl)malonic acid diethyl ester (40.0 g), 4-bromo-2-fluorobenzylamine hydrochloride (29.0 g) and triethylamine (54.8 g, 75.0 ml) in anhydrous dimethylformamide (100 ml) was stirred under the stream of nitrogen at 70° C. for 1 hour. After cooling, the reaction mixture was poured into 5% hydrochloric acid and extracted with ethyl acetate. The extracts were dried over anhydrous sodium sulfate and evaporated under reduced pressure. The residue was recrystallized from ethyl acetate/n-hexane to give the title compound (38.0 g, 86.0%) as colorless crystals, mp 114°-115° C.

Workup

  1. temperatureAfter cooling
  2. extractionextracted with ethyl acetate
  3. dry with materialThe extracts were dried over anhydrous sodium sulfate
  4. customevaporated under reduced pressure
  5. customThe residue was recrystallized from ethyl acetate/n-hexane

Sources & evidence

ORD record
ord-2677d88f6e734862823cfcff8a75a7bb
Source dataset
uspto-grants-1993_11
Patent number
US05258382

Reaction notes

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