Acetic Acid → HCID 136381080, compound

HRID 976252Notes

Reaction equation

HRID 976252 reaction equation
[CH3:1][N:2]1[C:6]([CH2:7][C:8]([O:10][CH3:11])=[O:9])=[C:5]([O:12][C:13]2[CH:18]=[C:17]([O:19][C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=3[F:26])[N:16]=[CH:15][N:14]=2)[C:4]([CH3:27])=[N:3]1.[CH:28](OC)=[O:29].[H-].[Na+].C(O)(=O)C>CN(C)C=O>[CH3:11][O:10][C:8](=[O:9])/[C:7](/[C:6]1[N:2]([CH3:1])[N:3]=[C:4]([CH3:27])[C:5]=1[O:12][C:13]1[CH:18]=[C:17]([O:19][C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=2[F:26])[N:16]=[CH:15][N:14]=1)=[CH:28]/[OH:29]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 7865Methyl formateHCID 24758Sodium hydrideHCID 53724169HCID 53724169, compound

Product 1

HCID 136381080HCID 136381080, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

A solution of 3.5 g (9.3 mmol) of methyl {1,3-dimethyl-4-[6-(2-fluorophenoxy)pyrimidin-4-yloxy]pyrazol-5-yl}acetate and 10 ml of methyl formate in 10 ml of dimethyl formamide is slowly added dropwise to a suspension of 0.5 g (20.0 mmol) of sodium hydride (95%) in 40 ml of dimethyl formamide, while keeping the temperature below 30° C. The reaction mixture is stirred for 2 hours at room temperature, acidified with acetic acid and, after addition of 200 ml of ice-water, extracted with 200 ml of ethyl acetate. The organic phase is washed with water and sodium chloride solution, dried and concentrated under vacuum, giving E-methyl-2-{1,3-dimethyl-4-[6-(2-fluorophenoxy)pyrimidin-4-yloxy]pyrazol-5-yl}-3-hydroxyacrylate as a brown resin, which is stirred together with 1.8 g (13.0 mmol) of potassium carbonate and 0.9 ml (6.7 mmol) of dimethyl sulfate in 40 ml of acetone for 3 hours at room temperature. The reaction mixture is filtered, the filtrate is diluted with 50 ml of water and extracted with 100 ml of ethyl acetate. The organic phase is washed with sodium chloride solution, dried and concentrated under vacuum. The residue is chromatographed over silica gel tetrahydrofuran/n-hexane (1:1) as eluant, giving E-methyl-2-{1,3-dimethyl-4-[6-(2-fluorophenoxy)pyrimidin-4-yloxy]pyrazol-5-yl}-3-methoxyacrylate as a yellow resin; MS: 414 (M+, 44%), 75 (100).

Workup

  1. customthe temperature below 30° C
  2. extractionextracted with 200 ml of ethyl acetate
  3. washThe organic phase is washed with water and sodium chloride solution
  4. customdried
  5. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-4b5093890d9e4abba86777798378ea8b
Source dataset
uspto-grants-1997_03
Patent number
US05612338

Reaction notes

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