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

HRID 256589Notes

Reaction equation

HRID 256589 reaction equation
[CH:1]1([CH3:30])[CH2:6][CH2:5][CH:4]([CH:7]([CH3:9])[CH3:8])[CH:3]([O:10][C:11](=[O:29])[CH:12]([N:18]2[CH:22]=[CH:21][CH:20]=[C:19]2[C:23](=[O:28])C(Cl)(Cl)Cl)[C:13](OCC)=[O:14])[CH2:2]1.Cl.[Br:32][C:33]1[CH:40]=[CH:39][C:36]([CH2:37][NH2:38])=[C:35]([F:41])[CH:34]=1.C(N(CC)CC)C>CN(C)C=O>[CH:1]1([CH3:30])[CH2:6][CH2:5][CH:4]([CH:7]([CH3:8])[CH3:9])[CH:3]([O:10][C:11]([CH:12]2[N:18]3[CH:22]=[CH:21][CH:20]=[C:19]3[C:23](=[O:28])[N:38]([CH2:37][C:36]3[CH:39]=[CH:40][C:33]([Br:32])=[CH:34][C:35]=3[F:41])[C:13]2=[O:14])=[O:29])[CH2:2]1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 184681974-Bromo-2-fluorobenzylamine hydrochlorideHCID 536822462-(2-Trichloroacetylpyrrol-1-yl)malonic acid ethyl (-)-menthyl ester

Product 1

HCID 867473472-(4-Bromo-2-fluorobenzyl)-1,3-dioxo-1,2,3,4-tetrahydropyrrolo[1,2-a]pyrazine-4-carboxylic acid (-)-menthyl esterYield 78.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
75 °C

Procedure

A mixture of 2-(2-trichloroacetylpyrrol-1-yl)malonic acid ethyl (-)-menthyl ester (87.0 g), 4-bromo-2-fluorobenzylamine hydrochloride (53.0 g) and triethylamine (66.4 g, 91.0 ml) in anhydrous dimethylformamide (200 ml) was stirred under the stream of nitrogen at 75° C. for 2 hours. The reaction mixture was concentrated under reduced pressure and the residue was dissolved in ethyl acetate. The solution was washed with 5% cold hydrochloric acid and then with saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, and evaporated under reduced pressure. The residue was recrystallized from methanol to give the title compound (74.0 g, 78.7%) as colorless crystals, mp 98°-99° C.

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. dissolutionthe residue was dissolved in ethyl acetate
  3. washThe solution was washed with 5% cold hydrochloric acid
  4. dry with materialwith saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate
  5. customevaporated under reduced pressure
  6. customThe residue was recrystallized from methanol

Sources & evidence

ORD record
ord-efe1eeb916da40f484cf2a3149a501c1
Source dataset
uspto-grants-1993_11
Patent number
US05258382

Reaction notes

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