1,2-Dichloroethane → methyl (2S,4E)-4-methoxyimino-1-[4-(2-methylphenyl)benzoyl]pyrrolidine-2-carboxylate

HRID 457922Notes

Reaction equation

HRID 457922 reaction equation
[CH3:1][O:2][C:3]([C@@H:5]1[CH2:9][C:8](=[N:10][O:11][CH3:12])[CH2:7][NH:6]1)=[O:4].[CH3:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=1[C:20]1[CH:25]=[CH:24][C:23]([C:26](O)=[O:27])=[CH:22][CH:21]=1.C(Cl)Cl.C(Cl)CCl>CN(C)C1C=CN=CC=1.CN(C=O)C>[CH3:12][O:11]/[N:10]=[C:8]1\[CH2:9][C@@H:5]([C:3]([O:2][CH3:1])=[O:4])[N:6]([C:26]([C:23]2[CH:22]=[CH:21][C:20]([C:15]3[CH:16]=[CH:17][CH:18]=[CH:19][C:14]=3[CH3:13])=[CH:25][CH:24]=2)=[O:27])[CH2:7]\1

Participants

7

Reactant 4

HCID 111,2-DichloroethaneHCID 6344DichloromethaneHCID 27598152'-Methyl-biphenyl-4-carboxylic acidHCID 123256627methyl-(2S,4EZ)-4-(methoxyimino)2-pyrrolidinecarboxylate

Product 1

HCID 10109472methyl (2S,4E)-4-methoxyimino-1-[4-(2-methylphenyl)benzoyl]pyrrolidine-2-carboxylateYield 22%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolvent

Procedure

Method A (e.g. methyl (2S,4EZ)-4-4-(methoxyimino-1-[(2′-methyl[1,1′-biphenyl]-4-yl)carbonyl]-2-pyrrolidinecarboxylate): A solution of methyl-(2S,4EZ)-4-(methoxyimino)-2-pyrrolidinecarboxylate (0.564 g, 3.28 mmol), 2′-methyl[1,1′-biphenyl]-4-carboxylic acid (0.765 g, 3.60 mmol) and 4-dimethylaminopyridine (0.880 g, 7.21 mmol) in a 7:3 mixture of DCM and DMF (30 ml) was made. EDC (0.691 mg, 3.60 mmol) was added slowly at 0° C. The reaction mixture was stirred overnight at r.t. It was washed with water (twice 20 ml), dried over MgSO4, filtrated and evaporated in vacuo. The resulting crude product mixture, methyl (2S,4EZ)-4-(methoxyimino)-1-[(2′-methyl[1,1′-biphenyl]-4-yl)carbonyl]-2-pyrrolidinecarboxylate, was purified by flash chromatography, unsing cyclohexane/EtOAc 8:2 as eluent. After several further chromatographies, (E)- and (Z)-isomers could be separated: methyl (2S,4E)-4-(methoxyimino)-1-[(2′-methyl[1,1′-biphenyl]-4-yl)carbonyl]-2-pyrrolidinecarboxylate (261 mg, 22%) was isolated as a colorless powder in 98.3% purity by HPLC, and methyl (2S,4Z)-4-(methoxyimino)-1-[(2′-methyl[1,1′-biphenyl]-4-yl)carbonyl]-2-pyrrolidinecarboxylate (237 mg, 20%) was isolated as a colorless powder in 98.3% purity by HPLC.

Workup

  1. washIt was washed with water (twice 20 ml)
  2. dry with materialdried over MgSO4
  3. filtrationfiltrated
  4. customevaporated in vacuo
  5. customThe resulting crude product mixture, methyl (2S,4EZ)-4-(methoxyimino)-1-[(2′-methyl[1,1′-biphenyl]-4-yl)carbonyl]-2-pyrrolidinecarboxylate, was purified by flash chromatography, unsing cyclohexane/EtOAc 8:2 as eluent
  6. customAfter several further chromatographies, (E)- and (Z)-isomers could be separated

Sources & evidence

ORD record
ord-3a8560e12327401a981174c837567654
Source dataset
uspto-grants-2007_03
Patent number
US07189754B2

Reaction notes

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