Carbamimidic acid, methyl ester, sulfate (1:1) → HCID 178498443, compound

HRID 1452654Notes

Reaction equation

HRID 1452654 reaction equation
[C:1](/[C:4](=[CH:9]/[C:10]1[CH:15]=[CH:14][C:13]([F:16])=[CH:12][CH:11]=1)/[C:5]([O:7][CH3:8])=[O:6])(=O)[CH3:2].S(O)(O)(=O)=O.[CH3:22][O:23][C:24](=[NH:26])[NH2:25].C([O-])(O)=O.[Na+]>C(O)C>[F:16][C:13]1[CH:14]=[CH:15][C:10]([CH:9]2[NH:26][C:24]([O:23][CH3:22])=[N:25][C:1]([CH3:2])=[C:4]2[C:5]([O:7][CH3:8])=[O:6])=[CH:11][CH:12]=1

Participants

5

Reactant 3

HCID 169039Carbamimidic acid, methyl ester, sulfate (1:1)HCID 516892Sodium BicarbonateHCID 10751489methyl (2Z)-2-acetyl-3-(4-fluorophenyl)-2-propenoate

Product 1

HCID 178498443HCID 178498443, compound

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A mixture of methyl (2Z)-2-acetyl-3-(4-fluorophenyl)-2-propenoate (0.220 mole, 48.8 g), O-methyl isourea hydrogensulfate (53.40 g, 0.310 mol, 1.5 eq.), NaHCO3 (61.74 g, 0.74 mole, 3.5 equiv.) and ethanol (1.2 L) was refluxed for 24 h, cooled to room temperature, and filtered. The solid was washed with ethanol (200 mL) and the combined filtrate was concentrated in vacuo. The residue was purified by chromatography (silica gel, hexanes/EtOAc/Et3N 50:50:0.1) to yield a mixture of tautomers (4:1, 33.0 g, 53.9%). 1H NMR (CDCl3) δ 7.32-7.24 (m, 2H), 7.04-6.95 (m, 2H), 5.81 (s, 1H), 5.38 (d, 1H, J=2.9 Hz), 4.00 (s, 3H), 3.63 (s, 3H), 2.34 (s, 3H).

Workup

  1. temperaturewas refluxed for 24 h
  2. filtrationfiltered
  3. washThe solid was washed with ethanol (200 mL)
  4. concentrationthe combined filtrate was concentrated in vacuo
  5. customThe residue was purified by chromatography (silica gel, hexanes/EtOAc/Et3N 50:50:0.1)
  6. customto yield
  7. additiona mixture of tautomers (4:1, 33.0 g, 53.9%)

Sources & evidence

ORD record
ord-960bda8449c34f0fade8e1af02e30c9b
Source dataset
uspto-grants-2009_01
Patent number
US07473698B2

Reaction notes

Loading…