Sodium hydride → (1-(4-oxopentyl)-1H-benzimidazol-2-yl)(1-(t-butoxycarbonyl)piperidin-4-yl)amine

HRID 323345

반응식

HRID 323345 반응식
[NH:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[NH:10][CH:11]1[CH2:16][CH2:15][N:14]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:13][CH2:12]1.[H-].[Na+].Cl[CH2:27][CH2:28][CH2:29][C:30](=[O:32])[CH3:31].[Cl-].[NH4+]>[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.C(=O)(O)[O-].[Na+].CO.ClCCl.CN(C)C=O.O1CCCC1>[O:32]=[C:30]([CH3:31])[CH2:29][CH2:28][CH2:27][N:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[NH:10][CH:11]1[CH2:16][CH2:15][N:14]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:13][CH2:12]1

참가 물질

10

반응물 4

HCID 24758Sodium hydride2회HCID 25517Ammonium ChlorideHCID 799932-Pentanone, 5-chloro-2회HCID 22036999HCID 22036999, 화합물

생성물 1

HCID 22009233(1-(4-oxopentyl)-1H-benzimidazol-2-yl)(1-(t-butoxycarbonyl)piperidin-4-yl)amine

시약·촉매·용매 5

HCID 74236Tetrabutylammonium Bromide촉매HCID 6228Dimethylformamide용매HCID 8028Tetrahydrofuran용매HCID 516892Sodium Bicarbonate용매HCID 21226129Dichloromethane methanol용매

실험 절차

Combine (1H-benzimidazol-2-yl)(1-(t-butoxycarbonyl)piperidin-4-yl)amine (3.5 mmol) and tetrahydrofuran (45 mL) and dimethylformamide (5 mL). Cool in an ice bath and add sodium hydride (0.21 g, 60% in oil, 5.22 mmol). After 1 hour, add 5-chloropentan-2-one, ethylene ketal (0.79 mL, 5.22 mmol) and tetra-n-butylammonium bromide (112 mg, 0.35 mmol) and warm to ambient temperature. Heat to reflux. After 18 hours, cool, add sodium hydride (0.1 g) and 5-chloropentan-2-one, ethylene ketal (0.50 mL) and again heat to reflux. After 24 hours, cool in a dry-ice/acetone bath and add a saturated aqueous solution of ammonium chloride. Warm to ambient temperature and dilute the reaction mixture with a saturated aqueous solution of sodium bicarbonate. Concentrate in vacuo to remove most to the tetrahydrofuran and extract three times with ethyl acetate. Extract the combined organic layers with water and then brine, dry the organic layer over Na2SO4, filter, and evaporate in vacuo to give a residue. Chromatograph the residue on silica gel eluting with 5% methanol/dichloromethane/0.1% saturated aqueous ammonia solution to give (1-(4-oxopentyl)-1H-benzimidazol-2-yl)(1-(t-butoxycarbonyl)piperidin-4-yl)amine, ethylene ketal.

후처리

  1. temperatureCool in an ice bath
  2. temperatureHeat to reflux
  3. waitAfter 18 hours
  4. temperaturecool
  5. temperatureagain heat to reflux
  6. waitAfter 24 hours
  7. temperaturecool in a dry-ice/acetone bath
  8. temperatureWarm to ambient temperature
  9. concentrationConcentrate in vacuo
  10. customto remove most to the tetrahydrofuran
  11. extractionextract three times with ethyl acetate
  12. extractionExtract the combined organic layers with water
  13. dry with materialbrine, dry the organic layer over Na2SO4
  14. filtrationfilter
  15. customevaporate in vacuo
  16. customto give a residue

출처 및 근거

ORD 기록
ord-d89fd8746f344cdc9a54815184619c2f
출처 데이터셋
uspto-grants-2001_04
특허 번호
US06211199B1

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