Carbon tetrabromide → 5-Bromo-4-(bromomethyl)-2-(methylthio)pyrimidine

HRID 604679노트

반응식

HRID 604679 반응식
[Br:1][C:2]1[C:3]([CH2:10]O)=[N:4][C:5]([S:8][CH3:9])=[N:6][CH:7]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(Br)(Br)(Br)[Br:32]>C(Cl)Cl>[Br:1][C:2]1[C:3]([CH2:10][Br:32])=[N:4][C:5]([S:8][CH3:9])=[N:6][CH:7]=1

참가 물질

5

반응물 3

HCID 11205Carbon tetrabromideHCID 11776TriphenylphosphineHCID 66524860(5-Bromo-2-(methylthio)pyrimidin-4-yl)methanol

생성물 1

HCID 150630115-Bromo-4-(bromomethyl)-2-(methylthio)pyrimidine

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

To a cold (0° C.) solution of [5-bromo-2-(methylthio)pyrimidin-4-yl]methanol (Step 13, 2.20 g, 9.34 mmol) in CH2Cl2 (46.7 mL) was added triphenylphosphine (3.19 g, 12.14 mmol) followed by carbon tetrabromide (4.03 g, 12.14 mmol). The resulting mixture was stirred cold for 1 h. LCMS trace of the aliquot indicated completion of reaction. Volatiles were removed under reduced pressure. Half of the crude material was purified by flash chromatography (SiO2, Biotage 40M cartridge). The column was eluted with an isocratic acetone/hexanes mixture (2.5%, v/v). No purification was obtained. All fractions and reaction crude were combined and purified by preparative HPLC (Kromasil 100-5C18, 100×21.1 mm) eluting with MeCN/water+0.1% TFA (51% to 62% organic in 10 min, hold 62% for 2 min, 20 mL/min). Related fractions were combined and evaporated under reduced pressure. The desired compound azeotroped with the water and was extracted with EtOAc, washed with brine, dried (Na2SO4), filtered and concentrated to afford a light brown oil as the titled compound. LCMS calc.=297.86; found=298.87.

후처리

  1. customcompletion of reaction
  2. customVolatiles were removed under reduced pressure
  3. customHalf of the crude material was purified by flash chromatography (SiO2, Biotage 40M cartridge)
  4. washThe column was eluted with an isocratic acetone/hexanes mixture (2.5%, v/v)
  5. customNo purification
  6. customwas obtained
  7. customAll fractions and reaction crude
  8. custompurified by preparative HPLC (Kromasil 100-5C18, 100×21.1 mm)
  9. washeluting with MeCN/water+0.1% TFA (51% to 62% organic in 10 min, hold 62% for 2 min, 20 mL/min)
  10. customevaporated under reduced pressure
  11. customThe desired compound azeotroped with the water
  12. extractionwas extracted with EtOAc
  13. washwashed with brine
  14. dry with materialdried (Na2SO4)
  15. filtrationfiltered
  16. concentrationconcentrated

출처 및 근거

ORD 기록
ord-bcdd2c70a9434d5d9d974e2fe12e8104
출처 데이터셋
uspto-grants-2011_03
특허 번호
US07910592B2

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