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

HRID 604679ノート

反応式

HRID 604679 の反応式
[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

参加物

5

反応物 3

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

生成物 1

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

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-bcdd2c70a9434d5d9d974e2fe12e8104
出典データセット
uspto-grants-2011_03
特許番号
US07910592B2

反応ノート

読み込み中…