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

HRID 1748549노트

반응식

HRID 1748549 반응식
[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]

참가 물질

8

반응물 4

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

생성물 1

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

시약·촉매·용매 3

HCID 167845palladium(II) acetate촉매HCID 12976736Bis(ditert-butyl(cyclopenta-2,4-dien-1-yl)phosphane);iron(2+)촉매HCID 312751,4-Dioxane용매

실험 절차

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)+.

후처리

  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)

출처 및 근거

ORD 기록
ord-2baa615c565a4a658276282c6858386c
출처 데이터셋
uspto-grants-2015_10
특허 번호
US09150555B2

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