Ammonium Acetate → [(S)-1-(2-{(4-borono-phenyl)-[(E)-(3-phenylacryloyl)]amino}acetyl)pyrrolidin-3-yl]carbamic acid, tert-butyl ester

HRID 468605노트

반응식

HRID 468605 반응식
I([O-])(=O)(=O)=O.[Na+].C([O-])(=O)C.[NH4+].CC1(C)C(C)(C)[O:16][B:15]([C:20]2[CH:25]=[CH:24][C:23]([N:26]([C:43](=[O:52])/[CH:44]=[CH:45]/[C:46]3[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=3)[CH2:27][C:28]([N:30]3[CH2:34][CH2:33][C@H:32]([NH:35][C:36](=[O:42])[O:37][C:38]([CH3:41])([CH3:40])[CH3:39])[CH2:31]3)=[O:29])=[CH:22][CH:21]=2)[O:14]1>O.CC(C)=O>[B:15]([C:20]1[CH:21]=[CH:22][C:23]([N:26]([C:43](=[O:52])/[CH:44]=[CH:45]/[C:46]2[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=2)[CH2:27][C:28]([N:30]2[CH2:34][CH2:33][C@H:32]([NH:35][C:36](=[O:42])[O:37][C:38]([CH3:41])([CH3:40])[CH3:39])[CH2:31]2)=[O:29])=[CH:24][CH:25]=1)([OH:14])[OH:16]

참가 물질

6

반응물 3

HCID 517165Ammonium AcetateHCID 23667635Sodium periodateHCID 59212034[(S)-1-(2-{[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-[(E)-(3-phenylacryloyl)]amino}acetyl)pyrrolidin-3-yl]-carbamic acid, tert-butyl ester

생성물 1

HCID 59211964[(S)-1-(2-{(4-borono-phenyl)-[(E)-(3-phenylacryloyl)]amino}acetyl)pyrrolidin-3-yl]carbamic acid, tert-butyl ester수율 80%

시약·촉매·용매 2

HCID 180Acetone용매HCID 962Water용매

실험 절차

Sodium periodate (2.06 g, 9.6 mmol) and ammonium acetate (0.74 g, 9.6 mmol) in water (20 mL) were added to [(S)-1-(2-{[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-[(E)-(3-phenylacryloyl)]amino}acetyl)pyrrolidin-3-yl]-carbamic acid, tert-butyl ester 4 (1.85 g, 3.2 mmol) in acetone (30 mL) and the reaction stirred at room temperature for 64 h. The reaction mixture was concentrated in vacuo and 1M NaOH was added. The mixture was stirred for 4 h and then shaken with dichloromethane and filtered. The two layers were separated and the NaOH layer washed with dichloromethane. The aqueous basic layer was acidified to pH1 with conc. hydrochloric acid and extracted with ethyl acetate (×2). The combined organic layers were washed with brine, dried (Na2SO4) and evaporated to dryness. The resultant residue was purified by flash column chromatography on silica gel, eluting with ethyl acetate→5% methanol/ethyl acetate→10% methanol/ethyl acetate→methanol, to give the title compound as a glass (1.26 g, 80%) which was used directly in the next stage.

후처리

  1. concentrationThe reaction mixture was concentrated in vacuo and 1M NaOH
  2. additionwas added
  3. stirringThe mixture was stirred for 4 h
  4. stirringshaken with dichloromethane
  5. filtrationfiltered
  6. customThe two layers were separated
  7. washthe NaOH layer washed with dichloromethane
  8. extractionextracted with ethyl acetate (×2)
  9. washThe combined organic layers were washed with brine
  10. dry with materialdried (Na2SO4)
  11. customevaporated to dryness
  12. customThe resultant residue was purified by flash column chromatography on silica gel
  13. washeluting with ethyl acetate→5% methanol/ethyl acetate→10% methanol/ethyl acetate→methanol

출처 및 근거

ORD 기록
ord-989a82046c274a01974e3812b4b9c8ea
출처 데이터셋
uspto-grants-2014_01
특허 번호
US08624022B2

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