Butyl vinyl ether → N-[(1R)-1-(4-Acetylphenyl)ethyl]methanesulfonamide

HRID 880240

反応式

HRID 880240 の反応式
Br[C:2]1[CH:7]=[CH:6][C:5]([C@H:8]([NH:10][S:11]([CH3:14])(=[O:13])=[O:12])[CH3:9])=[CH:4][CH:3]=1.[CH:15]([O:17]CCCC)=[CH2:16].C(=O)([O-])[O-].[K+].[K+]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[C:15]([C:2]1[CH:7]=[CH:6][C:5]([C@H:8]([NH:10][S:11]([CH3:14])(=[O:13])=[O:12])[CH3:9])=[CH:4][CH:3]=1)(=[O:17])[CH3:16]

参加物

5

反応物 3

HCID 8108Butyl vinyl etherHCID 11430Potassium CarbonateHCID 28560458N-[(1R)-1-(4-bromophenyl)ethyl]methanesulfonamide

生成物 1

HCID 117774699N-[(1R)-1-(4-Acetylphenyl)ethyl]methanesulfonamide収率 70.1%

試薬・触媒・溶媒 1

HCID 167845palladium(II) acetate触媒

反応条件

温度
110 °C

実験手順

Charge a tube with N-[(1R)-1-(4-bromophenyl)ethyl]methanesulfonamide (29 g, 104 mmol), butyl vinyl ether (34.23 mL, 261 mmol), palladium(II) acetate (14.04 g, 63 mmol), bis-(1,3-diphenylphosphino)propane (52.7 g, 125 mmol) and potassium carbonate (17.3 g, 125 mmol). Degas the tube with nitrogen for 2 minutes, and then add H2O (69.5 mL) and DMF (69.5 mL). Seal the tube and stir at 110° C. for 20 h. Cool the reaction mixture to ambient temperature and add HCl (2N, 60 mL). Stir the mixture at ambient temperature for 10 min. Adjust the pH of the mixture to a pH of 7 using NaOH pellets; dilute with DCM (220 mL); filter through a Celite® pad; and sequentially wash the filtrate with aqueous K2CO3 (2×120 mL), brine (2×100 mL), and H2O (100 mL). Dry the mixture over MgSO4; filter; and concentrate the filtrate under reduced pressure to provide a residue. Purify the residue via flash column chromatography eluting with EtOAc in hexanes (step gradient of 0, 5, 10, 20, 30 and finally 40% EtOAc). Combine the product fractions and remove the solvents under reduced pressure to give the title compound (17.6 g, 70.0%) as a yellow oil. MS (m/z): 242 (M+1).

後処理

  1. customDegas the tube with nitrogen for 2 minutes
  2. customSeal the tube
  3. temperatureCool the reaction mixture to ambient temperature
  4. additionadd HCl (2N, 60 mL)
  5. stirringStir the mixture at ambient temperature for 10 min
  6. additiondilute with DCM (220 mL)
  7. filtrationfilter through a Celite® pad
  8. washand sequentially wash the filtrate with aqueous K2CO3 (2×120 mL), brine (2×100 mL), and H2O (100 mL)
  9. dry with materialDry the mixture over MgSO4
  10. filtrationfilter
  11. concentrationand concentrate the filtrate under reduced pressure
  12. customto provide a residue
  13. customPurify the residue via flash column chromatography
  14. washeluting with EtOAc in hexanes (step gradient of 0, 5, 10, 20, 30 and finally 40% EtOAc)
  15. customCombine the product fractions and remove the solvents under reduced pressure

出典と根拠

ORDレコード
ord-5b86283e349c4c14b138209983c3c967
出典データセット
uspto-grants-2015_03
特許番号
US08993568B2

関連ノート

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