Ammonium Chloride → 1-(5-cyclopropyl-3-fluoropyridin-2-yl)-5-methyl-1H-pyrazole-4-carboxylic acid ethyl ester

HRID 1748549Notes

Reaction equation

HRID 1748549 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[CH:7]=[N:8][N:9]([C:12]2[C:17]([F:18])=[CH:16][C:15](Cl)=[CH:14][N:13]=2)[C:10]=1[CH3:11])=[O:5])[CH3:2].[CH:20]1(B(O)O)[CH2:22][CH2:21]1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].[Cl-].[NH4+]>O1CCOCC1.C(P(C(C)(C)C)[C-]1C=CC=C1)(C)(C)C.[C-]1(P(C(C)(C)C)C(C)(C)C)C=CC=C1.[Fe+2].C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH2:1]([O:3][C:4]([C:6]1[CH:7]=[N:8][N:9]([C:12]2[C:17]([F:18])=[CH:16][C:15]([CH:20]3[CH2:22][CH2:21]3)=[CH:14][N:13]=2)[C:10]=1[CH3:11])=[O:5])[CH3:2]

Participants

8

Reactant 4

HCID 25517Ammonium ChlorideHCID 62657Potassium Phosphate, TribasicHCID 2760897Cyclopropylboronic acidHCID 46739259Ethyl 1-(5-chloro-3-fluoropyridin-2-yl)-5-methyl-1H-pyrazole-4-carboxylate

Product 1

HCID 866924971-(5-cyclopropyl-3-fluoropyridin-2-yl)-5-methyl-1H-pyrazole-4-carboxylic acid ethyl esterYield 92.2%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 12976736Bis(ditert-butyl(cyclopenta-2,4-dien-1-yl)phosphane);iron(2+)CatalystHCID 312751,4-DioxaneSolvent

Procedure

A suspension of 1-(5-chloro-3-fluoropyridin-2-yl)-5-methyl-1H-pyrazole-4-carboxylic acid ethyl ester (2 g) in Reference Example 124 (1), cyclopropylboronic acid (911 mg), 1,1′-bis(di-tert-butylphosphino)ferrocene (167 mg), palladium acetate (79 mg) and tripotassium phosphate (4.49 g) in 1,4-dioxane (16 ml) was stirred under reflux. After completion of the reaction, the mixture was allowed to cool, ice water and a saturated aqueous solution of ammonium chloride were added thereto, and the mixture was extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate, and the solvent was evaporated in vacuo. The obtained residue was purified with silica gel chromatography (n-hexane/ethyl acetate) to give 1-(5-cyclopropyl-3-fluoropyridin-2-yl)-5-methyl-1H-pyrazole-4-carboxylic acid ethyl ester (1.88 g) as a light brown oil. MS (ESI) m/z: 290 (M+H)+.

Workup

  1. temperatureunder reflux
  2. customAfter completion of the reaction
  3. temperatureto cool
  4. extractionthe mixture was extracted with ethyl acetate
  5. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  6. customthe solvent was evaporated in vacuo
  7. customThe obtained residue was purified with silica gel chromatography (n-hexane/ethyl acetate)

Sources & evidence

ORD record
ord-2baa615c565a4a658276282c6858386c
Source dataset
uspto-grants-2015_10
Patent number
US09150555B2

Reaction notes

Loading…