Water → 1-[4-(2-Aminopyridin-4-yloxy)-2-fluorophenylcarbamoyl]cyclopropanecarboxylic acid benzyl ester

HRID 1712662Notes

Reaction equation

HRID 1712662 reaction equation
[CH2:1]([O:8][C:9]([C:11]1([C:14](=[O:33])[NH:15][C:16]2[CH:21]=[CH:20][C:19]([O:22][C:23]3[CH:28]=[CH:27][N:26]=[C:25](C(=O)N)[CH:24]=3)=[CH:18][C:17]=2[F:32])[CH2:13][CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.O.C(O)(=O)C.C(O)(=O)C.IC1C=CC=CC=1.C[N:51](C)C=O>>[CH2:1]([O:8][C:9]([C:11]1([C:14](=[O:33])[NH:15][C:16]2[CH:21]=[CH:20][C:19]([O:22][C:23]3[CH:28]=[CH:27][N:26]=[C:25]([NH2:51])[CH:24]=3)=[CH:18][C:17]=2[F:32])[CH2:12][CH2:13]1)=[O:10])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 4

HCID 962Water2×HCID 6228DimethylformamideHCID 12217721Iodo benzene diacetateHCID 247884991-[4-(2-Carbamoylpyridin-4-yloxy)-2-fluorophenylcarbamoyl]cyclopropanecarboxylic acid benzyl ester

Product 1

HCID 594597071-[4-(2-Aminopyridin-4-yloxy)-2-fluorophenylcarbamoyl]cyclopropanecarboxylic acid benzyl ester

Procedure

1-[4-(2-Carbamoylpyridin-4-yloxy)-2-fluorophenylcarbamoyl]-cyclopropanecarboxylic acid benzyl ester (2 g) was dissolved in N,N-dimethylformamide (20 ml) at room temperature, and water (0.481 ml) was added. Iodobenzene diacetate (2.87 g) was added at room temperature with stirring, and the reaction mixture was stirred for 2.5 hours. Water (40 ml) was added to the reaction mixture, and the reaction was quenched by the addition of a 2N aqueous solution of sodium hydroxide until pH became 11and ethyl acetate was added and the layers were separated. The organic layer was washed with water and a 5% aqueous solution of sodium chloride, dried over magnesium sulfate, filtered, and concentrated. The resultant crude brown oil was purified by silica gel column chromatography (eluent; heptane:ethyl acetate=1:1, then 1:2) to give the title compound (819 mg) as cream crystals.

Workup

  1. stirringthe reaction mixture was stirred for 2.5 hours
  2. customthe reaction was quenched by the addition of a 2N aqueous solution of sodium hydroxide until pH
  3. additionwas added
  4. customthe layers were separated
  5. washThe organic layer was washed with water
  6. dry with materiala 5% aqueous solution of sodium chloride, dried over magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe resultant crude brown oil was purified by silica gel column chromatography (eluent

Sources & evidence

ORD record
ord-627f511d69e4447484e39f3e3ad51446
Source dataset
uspto-grants-2010_09
Patent number
US07790885B2

Reaction notes

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