Ammonia → cis-6-(4-Methoxy-2,3-dimethylphenyl)hexahydropyrrolo[1,2-a]pyrazine-1,4-dione

HRID 851958Notes

Reaction equation

HRID 851958 reaction equation
C([O:3][C:4]([C@H:6]1[CH2:10][CH2:9][C@@H:8]([C:11]2[CH:16]=[CH:15][C:14]([O:17][CH3:18])=[C:13]([CH3:19])[C:12]=2[CH3:20])[N:7]1[C:21](=[O:24])[CH2:22]Cl)=O)C.[NH3:25]>CO.O>[CH3:18][O:17][C:14]1[CH:15]=[CH:16][C:11]([C@H:8]2[N:7]3[C:21](=[O:24])[CH2:22][NH:25][C:4](=[O:3])[C@@H:6]3[CH2:10][CH2:9]2)=[C:12]([CH3:20])[C:13]=1[CH3:19]

Participants

5

Reactant 2

HCID 222AmmoniaHCID 69445732cis-1-(2-Chloroacetyl)-5-(4-methoxy-2,3-dimethylphenyl)pyrrolidine-2-carboxylic acid ethyl ester

Product 1

HCID 69384219cis-6-(4-Methoxy-2,3-dimethylphenyl)hexahydropyrrolo[1,2-a]pyrazine-1,4-dione

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Procedure

A mixture of the crude cis-1-(2-chloroacetyl)-5-(4-methoxy-2,3-dimethyl-phenyl)pyrrolidine-2-carboxylic acid ethyl ester (˜16.56 mmol) and ca. 7 M NH3 in MeOH (50 mL) is stirred in a sealed flask at room temperature for 2.5 days. The mixture is then diluted with water (ca. 200-300 mL). The resulting suspension is cooled to 0° C. and stirred well. The mixture is then filtered and the solid thoroughly washed with water followed by Et2O. Drying affords cis-6-(4-methoxy-2,3-dimethylphenyl)hexahydropyrrolo[1,2-a]pyrazine-1,4-dione as a slightly off-white powder. 1H NMR (CDCl3, 400 MHz): 6.70 (br, 1H), 6.68 (d, J=8.6 Hz, 1H), 6.64 (d, J=8.6 Hz, 1H), 5.38 (d, J=8.8 Hz, 1H), 4.29 (dd, J=10.8, 6.4 Hz, 1H), 4.10, 3.93 (ABXq, JAB=16.8 Hz, JAX=1.0 Hz, JBX=4.8 Hz, 2H), 3.77 (s, 3H), 2.43-2.31 (m, 1H), 2.26 (s, 3H), 2.24-2.11 (m, 2H), 2.16 (s, 3H), 1.85 (dd, J=12.2, 5.8 Hz, 1H). Electrospray MS: m/z 289 [M+1].

Workup

  1. temperatureThe resulting suspension is cooled to 0° C.
  2. stirringstirred well
  3. filtrationThe mixture is then filtered
  4. washthe solid thoroughly washed with water
  5. customDrying

Sources & evidence

ORD record
ord-023c75c7e3ac458fa059cf22ba81ac16
Source dataset
uspto-grants-2007_08
Patent number
US07253168B2

Reaction notes

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