Carbamimidic acid, methyl ester, sulfate (1:1) → HCID 178498444, compound

HRID 650570Notes

Reaction equation

HRID 650570 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:9]=[C:10]([C:15](=O)[CH3:16])[C:11]([O:13][CH3:14])=[O:12])[CH:5]=[CH:6][C:7]=1[F:8].S(O)(O)(=O)=O.[CH3:23][O:24][C:25](=[NH:27])[NH2:26].C([O-])(O)=O.[Na+]>CN(C=O)C.CCOC(C)=O>[F:1][C:2]1[CH:3]=[C:4]([CH:9]2[NH:27][C:25]([O:24][CH3:23])=[N:26][C:15]([CH3:16])=[C:10]2[C:11]([O:13][CH3:14])=[O:12])[CH:5]=[CH:6][C:7]=1[F:8]

Participants

6

Reactant 3

HCID 169039Carbamimidic acid, methyl ester, sulfate (1:1)HCID 516892Sodium BicarbonateHCID 54038767Methyl 2-{(3,4-difluorophenyl)methylene}-3-oxobutyrate

Product 1

HCID 178498444HCID 178498444, compoundYield 35.2%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
70 °C

Procedure

A mixture of methyl 2-{(3,4-difluorophenyl)methylene}-3-oxobutyrate (8.8 g, 36.6 mmol), O-methylisourea hydrogen sulfate (9.4 g, 55 mmol), and NaHCO3 (12.3 g, 0.146 mol) in DMF (30 mL) was stirred and heated at 70° C. for 16 hours. The mixture was cooled, diluted with EtOAc (300 mL) and washed with water (5×300 mL), brine (300 mL), and dried (MgSO4). Solvent was evaporated and the crude product was purified by flash column chromatography on silica gel using 10% through 20% EtOAc in hexane as the gradient eluent, to leave the product as an oil (3.82 g, 30.2%); 1H-NMR (CDC13): δ 2.32,2.39 (2 s, 3 H), 3.58, 3.64 (2 s, 3 H), 3.72, 3.85 (2 s, 3 H), 5.55 ( s, 1H), 6.13-7.8 (m, 4 H).

Workup

  1. temperatureThe mixture was cooled
  2. washwashed with water (5×300 mL), brine (300 mL)
  3. dry with materialdried (MgSO4)
  4. customSolvent was evaporated
  5. customthe crude product was purified by flash column chromatography on silica gel using 10% through 20% EtOAc in hexane as the gradient eluent

Sources & evidence

ORD record
ord-f7b5d0ed0c464969b821b7888120b142
Source dataset
uspto-grants-2001_08
Patent number
US06274585B1

Reaction notes

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