Methanol → HCID 59772744, compound

HRID 2220459Notes

Reaction equation

HRID 2220459 reaction equation
COC([C:5]1[N:6]([CH2:22][CH2:23][F:24])[CH:7]=[C:8]([C:10](=O)[C:11]([C:13]2[CH:18]=[CH:17][C:16]([F:19])=[C:15]([Br:20])[CH:14]=2)=O)C=1)=O.Cl.[CH3:26][NH:27][C:28]([NH2:30])=[NH:29].[C:31]([O-:34])([O-])=[O:32].[Na+].[Na+].CCO[C:40](C)=[O:41].[CH3:43]O>O1CCOCC1.O.CO.CCOC(C)=O>[CH3:43][O:34][C:31]([C:7]1[N:6]([CH2:22][CH2:23][F:24])[CH:5]=[C:10]([C:11]2([C:13]3[CH:18]=[CH:17][C:16]([F:19])=[C:15]([Br:20])[CH:14]=3)[C:40](=[O:41])[N:27]([CH3:26])[C:28]([NH2:30])=[N:29]2)[CH:8]=1)=[O:32]

Participants

9

Reactant 5

HCID 887MethanolHCID 8857Ethyl AcetateHCID 10340Sodium CarbonateHCID 59772681HCID 59772681, compoundHCID 178485118HCID 178485118, compound

Product 1

HCID 59772744HCID 59772744, compoundYield 76%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 312751,4-DioxaneSolventHCID 21584119Ethylacetate methanolSolvent

Procedure

To a solution of 0.742 gm (1.85 mmol) of 4-[2-(3-bromo-4-fluoro-phenyl)-2-oxo-acetyl]-1-(2-fluoro-ethyl)-1H-pyrrole-2-carboxylic acid methyl ester in 18 mL of MeOH and 21 mL of dioxane in a pressure tube was added 0.40 gm (3.7 mmol) of N-methylguanidine hydrochloride. After stirring at room temperature for 15 min, 0.41 gm (3.9 mmol) of Na2CO3 in 5.2 mL of H2O was added and the reaction mixture was sealed and heated to 85° C. for 4 h. The mixture was cooled and the solvents removed at reduced pressure. The residue was taken up in CH2Cl2 (200 mL) and washed with H2O (100 mL), saturated brine, dried (Na2SO4) and the solvent removed at reduced pressure. Chromatography on silica gel using a gradient of EtOAc to 3% MeOH-EtOAc yielded 0.64 gm (76% yield) of a white foam. 1H NMR (400 MHz, CDCl3) δ: 3.08 (s, 3H), 3.76 (s, 3H), 4.52 (m, 1H), 4.59 (m, 2H,), 4.71 (m, 1H), 6.92 (s, 1H), 6.94 (s, 1H), 7.04 (t, 1H, J=8.47 Hz), 7.50 (m, 1H), 8.28 (dd, 1H, J=2.2, 4.41 Hz).

Workup

  1. customthe reaction mixture was sealed
  2. temperatureheated to 85° C. for 4 h
  3. temperatureThe mixture was cooled
  4. customthe solvents removed at reduced pressure
  5. washwashed with H2O (100 mL), saturated brine
  6. dry with materialdried (Na2SO4)
  7. customthe solvent removed at reduced pressure

Sources & evidence

ORD record
ord-427c5297ce7345db88bfb1e0b4670869
Source dataset
uspto-grants-2008_08
Patent number
US07417047B2

Reaction notes

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