Sulfuric Acid → 5-Bromo-3-[(2,6-difluorobenzyl)oxy]pyridine-2-amine

HRID 1624074노트

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HRID 1624074 반응식
[F:1][C:2]1[CH:16]=[CH:15][CH:14]=[C:13]([F:17])[C:3]=1[CH2:4][O:5][C:6]1[C:7]([NH2:12])=[N:8][CH:9]=[CH:10][CH:11]=1.S(=O)(=O)(O)O.[Br:23]Br>C(O)(=O)C.C(OCC)(=O)C>[Br:23][C:10]1[CH:11]=[C:6]([O:5][CH2:4][C:3]2[C:13]([F:17])=[CH:14][CH:15]=[CH:16][C:2]=2[F:1])[C:7]([NH2:12])=[N:8][CH:9]=1

참가 물질

6

반응물 3

HCID 1118Sulfuric AcidHCID 24408BromineHCID 102634983-(2,6-Difluoro-benzyloxy)-pyridin-2-ylamine

생성물 1

HCID 211114885-Bromo-3-[(2,6-difluorobenzyl)oxy]pyridine-2-amine

시약·촉매·용매 2

HCID 176Acetic Acid용매HCID 8857Ethyl Acetate용매

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온도
0 °C

실험 절차

32.6 g of 3-[(2,6-difluorobenzyl)oxy]pyridine-2-amine (Example 4A; 138 mmol, 1 equivalent) were suspended in 552 ml of 10% strength sulphuric acid, and the mixture was cooled to 0° C. 8.5 ml of bromine (165 mmol, 1.2 equivalents) were dissolved in 85 ml of acetic acid and then, over a period of 90 min, added dropwise to the ice-cooled reaction solution. After the dropwise addition had ended, the mixture was stirred at 0° C. for 90 min and then diluted with 600 ml of ethyl acetate, and the aqueous phase was separated off. The aqueous phase was re-extracted with ethyl acetate and the organic phases were combined, washed with saturated aqueous sodium bicarbonate solution, dried and concentrated. The residue was dissolved in dichloromethane and chromatographed on silica gel (petroleum ether/ethyl acetate gradient as mobile phase). This gave 24 g (55% of theory) of the title compound. LC-MS (Method 1): Rt=0.96 min

후처리

  1. temperaturecooled
  2. customreaction solution
  3. additionAfter the dropwise addition
  4. customthe aqueous phase was separated off
  5. extractionThe aqueous phase was re-extracted with ethyl acetate
  6. washwashed with saturated aqueous sodium bicarbonate solution
  7. customdried
  8. concentrationconcentrated
  9. dissolutionThe residue was dissolved in dichloromethane
  10. customchromatographed on silica gel (petroleum ether/ethyl acetate gradient as mobile phase)

출처 및 근거

ORD 기록
ord-fc0f3bd793774287ae423a62a0b068f9
출처 데이터셋
uspto-grants-2014_07
특허 번호
US08778964B2

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