Pyridine → Dimethyl 2-(2-fluoro-4-(phenoxycarbonylamino)phenyl)malonate

HRID 1842960Notes

Reaction equation

HRID 1842960 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([C:13]([O:15][CH3:16])=[O:14])[C:9]([O:11][CH3:12])=[O:10])=[C:4]([F:17])[CH:3]=1.N1C=CC=CC=1.Cl[C:25]([O:27][C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)=[O:26]>CC(C)=O>[F:17][C:4]1[CH:3]=[C:2]([NH:1][C:25]([O:27][C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)=[O:26])[CH:7]=[CH:6][C:5]=1[CH:8]([C:9]([O:11][CH3:12])=[O:10])[C:13]([O:15][CH3:16])=[O:14]

Participants

5

Reactant 3

HCID 1049PyridineHCID 15891Phenyl chloroformateHCID 86672160Dimethyl 2-(4-amino-2-fluorophenyl)malonate

Product 1

HCID 86672161Dimethyl 2-(2-fluoro-4-(phenoxycarbonylamino)phenyl)malonateYield 78%

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Procedure

To a stirred solution of dimethyl 2-(4-amino-2-fluorophenyl)malonate (3.0 g, 12.448 mmol, 1.0 eq) in acetone (30 mL) was added pyridine (3.0 mL, 37.344 mmol, 3.0 eq) and phenyl chloroformate (1.89 mL, 14.937 mmol, 1.2 eq) at 0° C. and the mixture was stirred at RT for 1 h. The solvent was evaporated, the residue diluted with EtOAc (50 mL), washed with water (100 mL), brine (20 mL) and the solvent evaporated. The resulting residue was purified by CC using EtOAc/PE (1:4) as eluent to get dimethyl 2-(2-fluoro-4-(phenoxycarbonylamino)phenyl)malonate (3.5 g, 78%, white solid; TLC system: EtOAc/PE (3:7), Rf: 0.5).

Workup

  1. customThe solvent was evaporated
  2. additionthe residue diluted with EtOAc (50 mL)
  3. washwashed with water (100 mL), brine (20 mL)
  4. customthe solvent evaporated
  5. customThe resulting residue was purified by CC

Sources & evidence

ORD record
ord-9f2fe20525074ec98e6ec578089c77d7
Source dataset
uspto-grants-2015_02
Patent number
US08946204B2

Reaction notes

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