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

HRID 1748549ノート

反応式

HRID 1748549 の反応式
[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]

参加物

8

反応物 4

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

生成物 1

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

試薬・触媒・溶媒 3

HCID 167845palladium(II) acetate触媒HCID 12976736Bis(ditert-butyl(cyclopenta-2,4-dien-1-yl)phosphane);iron(2+)触媒HCID 312751,4-Dioxane溶媒

実験手順

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)+.

後処理

  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)

出典と根拠

ORDレコード
ord-2baa615c565a4a658276282c6858386c
出典データセット
uspto-grants-2015_10
特許番号
US09150555B2

反応ノート

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