Water → HCID 10337202, compound

HRID 1244604Notes

Reaction equation

HRID 1244604 reaction equation
[F:1][C:2]1[CH:3]=[C:4](/[CH:8]=[CH:9]/[C:10]2[CH:15]=[CH:14][C:13]([N:16]3[C:20](=[O:21])[CH2:19][CH:18]([C:22]([OH:24])=O)[CH2:17]3)=[CH:12][CH:11]=2)[CH:5]=[CH:6][CH:7]=1.S(Cl)(Cl)=O.[CH3:29][NH2:30].O>ClCCl.C(O)C>[CH3:29][NH:30][C:22]([CH:18]1[CH2:19][C:20](=[O:21])[N:16]([C:13]2[CH:14]=[CH:15][C:10](/[CH:9]=[CH:8]/[C:4]3[CH:5]=[CH:6][CH:7]=[C:2]([F:1])[CH:3]=3)=[CH:11][CH:12]=2)[CH2:17]1)=[O:24]

Participants

7

Reactant 4

HCID 962WaterHCID 6329MethylamineHCID 24386Thionyl ChlorideHCID 21920044HCID 21920044, compound

Product 1

HCID 10337202HCID 10337202, compoundYield 66%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 6344DichloromethaneSolvent3×

Conditions

Temperature
45 °C

Procedure

A suspension of 300 mg (0.92 mmol) of (E)-1-{4-[2-(3-fluoro-phenyl)-vinyl]-phenyl}-5-oxo-pyrrolidine-3-carboxylic acid in 5 ml of dichloromethane is treated with 549 mg (4.6 mmol) of thionylchloride and heated to 45° C. for 18 hours. Thereafter, the reaction mixture is evaporated to dryness under reduced pressure. The crude acid chloride obtained is dissolved in 5 ml of dry dichloromethane, then, at RT, 0.58 ml (4.61 mmol) of a solution of methylamine in ethanol (33%) is added and stirring continued for 3 hours. For the working-up, the reaction mixture is treated with water and dichloromethane. The organic layer is separated, dried over magnesium sulfate and evaporated. For purification, the crude product is chromatographed on silica gel using a 95:5-mixture of dichloromethane and methanol as the eluent. After crystallization from a mixture of dichloromethane and ether, there are obtained 207 mg (66% of theory) of (RS)-(E)-1-{4-[2-(3-fluoro-phenyl)-vinyl]-phenyl}-5-oxo-pyrrolidine-3-carboxylic acid methylamide as a light brown solid; MS: m/e=339 (M+H)+.

Workup

  1. customThereafter, the reaction mixture is evaporated to dryness under reduced pressure
  2. customThe crude acid chloride obtained
  3. customThe organic layer is separated
  4. dry with materialdried over magnesium sulfate
  5. customevaporated
  6. customFor purification
  7. customthe crude product is chromatographed on silica gel using a 95
  8. customAfter crystallization
  9. additionfrom a mixture of dichloromethane and ether, there

Sources & evidence

ORD record
ord-28da41221f6a428d9f3dd51c89312c03
Source dataset
uspto-grants-2006_10
Patent number
US07122562B2

Reaction notes

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