Methylamine → 3-{4-[(3-Fluorophenyl)methoxy]phenyl}-N-methylbut-2-enamide

HRID 2184371Notes

Reaction equation

HRID 2184371 reaction equation
[OH-].[K+].C[O:4][C:5](=O)[CH:6]=[C:7]([C:9]1[CH:14]=[CH:13][C:12]([O:15][CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[C:19]([F:23])[CH:18]=2)=[CH:11][CH:10]=1)[CH3:8].C(Cl)(=O)C(Cl)=O.[CH3:31][NH2:32]>CO.ClCCl.CN(C)C=O.C1COCC1>[CH3:31][NH:32][C:5](=[O:4])[CH:6]=[C:7]([C:9]1[CH:14]=[CH:13][C:12]([O:15][CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[C:19]([F:23])[CH:18]=2)=[CH:11][CH:10]=1)[CH3:8]

Participants

9

Reactant 4

HCID 6329MethylamineHCID 14797Potassium HydroxideHCID 65578Oxalyl chlorideHCID 69289443Methyl 3-{4-[(3-fluorophenyl)methoxy]phenyl}but-2-enoate

Product 1

HCID 692909953-{4-[(3-Fluorophenyl)methoxy]phenyl}-N-methylbut-2-enamideYield 50%

Reagents, catalysts & solvents 4

HCID 6228DimethylformamideCatalystHCID 887MethanolSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

0.224 g (4 mmol) of KOH is dissolved in 10 ml methanol. 0.4 g (1.33 mmol) of 3-[4-(3-fluoro-benzyloxy)-phenyl]-but-2-enoic acid methyl ester is added and the resulting solution refluxed for 6 hours, concentrated and acidified with 2N aqueous hydrochloric acid. Extraction with ethyl acetate gives 325 mg (85%) of the crude acid. This acid is dissolved in 10 ml of dichloromethane, 2 drops of N,N-dimethylformamide are added and the mixture is cooled to 0° C. Slow addition of 0.380 g (3 mmol) of oxalylchloride yields a yellow solution which is stirred for additional 1.5 hours at RT. Evaporation of the reaction mixture leaves a yellowish resin which is dissolved in 5 ml THF and slowly added at 0° C. to a mixture of 5 ml THF and 5 ml aqueous methylamine (40%). The resulting slurry is stirred at RT for 1 hour, evaporated, diluted with water and extracted three times with ethyl acetate. Chromatography on silica gel (cyclohexane/ethyl acetate 1:1) gives 220 mg (50%) of a colorless solid. MS: m/e=300.2 (M++H).

Workup

  1. temperaturethe resulting solution refluxed for 6 hours
  2. concentrationconcentrated
  3. extractionExtraction with ethyl acetate
  4. customgives 325 mg (85%) of the crude acid
  5. customyields a yellow solution which
  6. customEvaporation of the reaction mixture
  7. customleaves a yellowish resin which
  8. stirringThe resulting slurry is stirred at RT for 1 hour
  9. customevaporated
  10. additiondiluted with water
  11. extractionextracted three times with ethyl acetate

Sources & evidence

ORD record
ord-56c67f339c364a52b7219a081631f793
Source dataset
uspto-grants-2005_05
Patent number
US06900354B2

Reaction notes

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