Methanol → HCID 57908396, compound

HRID 425741Notes

Reaction equation

HRID 425741 reaction equation
[Cl:1][C:2]1[N:7]=[CH:6][C:5]([CH2:8][NH:9][C:10]2[CH2:14][O:13][C:12](=[O:15])[CH:11]=2)=[CH:4][CH:3]=1.[H-].[Na+].Br[CH2:19][CH:20]=[C:21]([Cl:23])[Cl:22].CO>O1CCCC1>[Cl:1][C:2]1[N:7]=[CH:6][C:5]([CH2:8][N:9]([CH2:19][CH:20]=[C:21]([Cl:23])[Cl:22])[C:10]2[CH2:14][O:13][C:12](=[O:15])[CH:11]=2)=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 887MethanolHCID 24758Sodium hydrideHCID 126424063-Bromo-1,1-dichloroprop-1-eneHCID 598435524-{[(6-Chloropyridin-3-yl)methyl]amino}furan-2(5H)-one

Product 1

HCID 57908396HCID 57908396, compoundYield 50.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

350 mg (1.56 mmol) of 4-[[(6-chloropyridin-3-yl)methyl]amino]furan-2(5H)-one (Ia-1; cf. EP 0539588 A1) and 124 mg (3.12 mmol) of a 60% dispersion of sodium hydride in mineral oil in 100 ml of tetrahydrofuran are heated under reflux for 3 h. After cooling to room temperature, 592 mg (3.12 mmol) of 3-bromo-1,1-dichloroprop-1-ene (cf. WO 8800183 A1) are added and the mixture is heated under reflux for a further 5 h. After cooling of the reaction mixture to room temperature and addition of methanol, the mixture is concentrated under reduced pressure. The residue is taken up in ethyl acetate and the mixture is washed successively twice with 1 N aqueous hydrochloric acid, twice with 1 N aqueous sodium hydroxide solution and once with saturated sodium chloride solution. The organic phase is then dried over sodium sulphate and concentrated under reduced pressure. Purification of the residue by column chromatography on silica gel (silica gel 60—Merck, particle size: 0.04 to 0.063 mm) using the mobile phase mixture ethyl acetate:cyclohexane (2:1) gives 264 mg (50% of theory) of 4-[[(6-chloropyridin-3-yl)methyl](3,3-dichloroprop-2-en-1-yl)amino]furan-2(5H)-one.

Workup

  1. temperatureunder reflux for 3 h
  2. temperaturethe mixture is heated
  3. temperatureunder reflux for a further 5 h
  4. temperatureAfter cooling of the reaction mixture to room temperature
  5. concentrationthe mixture is concentrated under reduced pressure
  6. washthe mixture is washed successively twice with 1 N aqueous hydrochloric acid, twice with 1 N aqueous sodium hydroxide solution and once with saturated sodium chloride solution
  7. dry with materialThe organic phase is then dried over sodium sulphate
  8. concentrationconcentrated under reduced pressure
  9. customPurification of the residue by column chromatography on silica gel (silica gel 60—Merck, particle size: 0.04 to 0.063 mm)

Sources & evidence

ORD record
ord-e22a454f7f1b451bb2b76175ec26bffe
Source dataset
uspto-grants-2012_01
Patent number
US08106211B2

Reaction notes

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