Dicyclohexylcarbodiimide → (2-acetyl-phenylamino)-phenyl-acetic acid (R)-(1-aza-bicyclo[2.2.2]oct-3-yl)ester

HRID 1255029노트

반응식

HRID 1255029 반응식
C1CCC(N=C=NC2CCCCC2)CC1.Cl.[C:17]([C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=1[NH:26][CH:27]([C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1)[C:28]([OH:30])=[O:29])(=[O:19])[CH3:18].C1C=CC2N(O)N=NC=2C=1.[N:47]12[CH2:54][CH2:53][CH:50]([CH2:51][CH2:52]1)[C@@H:49](O)[CH2:48]2>C1COCC1>[N:47]12[CH2:54][CH2:53][CH:50]([CH2:51][CH2:52]1)[C@@H:49]([O:29][C:28](=[O:30])[CH:27]([NH:26][C:21]1[CH:22]=[CH:23][CH:24]=[CH:25][C:20]=1[C:17](=[O:19])[CH3:18])[C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1)[CH2:48]2

참가 물질

6

반응물 4

HCID 10868DicyclohexylcarbodiimideHCID 757711-HydroxybenzotriazoleHCID 914043-Quinuclidinol, (-)-HCID 67424703(2-Acetyl-phenylamino)-phenyl-acetic acid hydrochloride

생성물 1

HCID 46840711(2-acetyl-phenylamino)-phenyl-acetic acid (R)-(1-aza-bicyclo[2.2.2]oct-3-yl)ester수율 107%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

실험 절차

PS-DCC (890 mg, 1.184 mmol, loading: 1.33 mmol/g) is suspended in dry THF (10 mL). (2-Acetyl-phenylamino)-phenyl-acetic acid hydrochloride (I63) (181 mg, 0.59 mmol), HOBt (181 mg, 1.18 mmol), and (R)-quinuclidin-3-ol (226 mg, 1.78 mmol) are added and the mixture is shaken at RT overnight. PS-DCC is filtered off and the filtrate is evaporated. The residue is dissolved in EtOAc and washed with sat. NaHCO3, water and brine, dried over Na2SO4, filtered and evaporated. The resulting crude oil is purified by flash chromatography (DCM/MeOH=9/1) to afford the title compound as a colorless oil (239 mg, quantitative yield, mixture of diastereoisomers).

후처리

  1. filtrationPS-DCC is filtered off
  2. customthe filtrate is evaporated
  3. dissolutionThe residue is dissolved in EtOAc
  4. washwashed with sat. NaHCO3, water and brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. customevaporated
  8. customThe resulting crude oil is purified by flash chromatography (DCM/MeOH=9/1)

출처 및 근거

ORD 기록
ord-c9cff036e205483fab009f36971b5205
출처 데이터셋
uspto-grants-2013_06
특허 번호
US08455646B2

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