5-Bromo-2-fluoropyridine → 1-Tert-butyl-4-(6-fluoropyridin-3-yl)piperazine

HRID 40703

반응식

HRID 40703 반응식
[C:1]([N:5]1[CH2:10][CH2:9][NH:8][CH2:7][CH2:6]1)([CH3:4])([CH3:3])[CH3:2].Br[C:12]1[CH:13]=[CH:14][C:15]([F:18])=[N:16][CH:17]=1.CC(C)([O-])C.[Na+].COC1C=CC=C(OC)C=1C1C=CC=CC=1P(C1CCCCC1)C1CCCCC1>C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C(OCC)(=O)C>[C:1]([N:5]1[CH2:10][CH2:9][N:8]([C:12]2[CH:17]=[N:16][C:15]([F:18])=[CH:14][CH:13]=2)[CH2:7][CH2:6]1)([CH3:4])([CH3:3])[CH3:2]

참가 물질

8

반응물 4

HCID 27831685-Bromo-2-fluoropyridineHCID 35305721-Tert-butylpiperazineHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 23676156Sodium t-butoxide

생성물 1

HCID 674121911-Tert-butyl-4-(6-fluoropyridin-3-yl)piperazine수율 71%

시약·촉매·용매 3

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 1140Toluene용매HCID 8857Ethyl Acetate용매

반응 조건

온도
80 °C

실험 절차

1-tert-Butylpiperazine (1.61 g, 11.4 mmol) is placed in 35 ml of toluene under nitrogen, 5-Bromo-2-fluoropyridine (2 g, 11.4 mmol), sodium t-butoxide (1.6 g, 17 mmol), tris(dibenzylideneacetone)dipalladium (0.52 g, 0.57 mmol), and S-Phos (0.93 g, 17 mmol) are then added. The reaction medium is heated at 80° C. for 18 h. After hydrolysis, and extraction with ethyl acetate, the organic phase is washed with water and then with a saturated aqueous sodium chloride solution. After drying over MgSO4, and concentrating to dryness, the crude product obtained is chromatographed on silica gel, elution being carried out with a gradient of methanol in dichloromethane ranging from 0% to 5%. 1.92 g of 1-tert-butyl-4-(6-fluoropyridin-3-yl)piperazine are obtained.

후처리

  1. washthe organic phase is washed with water
  2. dry with materialAfter drying over MgSO4
  3. concentrationconcentrating to dryness
  4. customthe crude product obtained
  5. customis chromatographed on silica gel, elution

출처 및 근거

ORD 기록
ord-1415b2b69aab4cb587315c27bb5ff3fe
출처 데이터셋
uspto-grants-2013_09
특허 번호
US08530477B2

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