Dicyclohexylcarbodiimide → (2,5-Dimethoxy-phenylamino)-phenyl-acetic acid (R)-(1-aza-bicyclo[2.2.2]oct-3-yl)ester

HRID 76992노트

반응식

HRID 76992 반응식
C1CCC(N=C=NC2CCCCC2)CC1.Cl.[CH3:17][O:18][C:19]1[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[CH:21][C:20]=1[NH:27][CH:28]([C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1)[C:29]([OH:31])=[O:30].C1C=CC2N(O)N=NC=2C=1.[N:48]12[CH2:55][CH2:54][CH:51]([CH2:52][CH2:53]1)[C@@H:50](O)[CH2:49]2>C1COCC1>[N:48]12[CH2:55][CH2:54][CH:51]([CH2:52][CH2:53]1)[C@@H:50]([O:30][C:29](=[O:31])[CH:28]([NH:27][C:20]1[CH:21]=[C:22]([O:25][CH3:26])[CH:23]=[CH:24][C:19]=1[O:18][CH3:17])[C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1)[CH2:49]2

참가 물질

6

반응물 4

HCID 10868DicyclohexylcarbodiimideHCID 757711-HydroxybenzotriazoleHCID 914043-Quinuclidinol, (-)-HCID 67425639(2,5-Dimethoxy-phenylamino)-phenyl-acetic acid hydrochloride

생성물 1

HCID 46840708(2,5-Dimethoxy-phenylamino)-phenyl-acetic acid (R)-(1-aza-bicyclo[2.2.2]oct-3-yl)ester수율 57%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

실험 절차

PS-DCC (715 mg, 0.951 mmol, loading: 1.33 mmol/g) is suspended in dry THF (10 mL). (2,5-Dimethoxy-phenylamino)-phenyl-acetic acid hydrochloride (I54) (154 mg, 0.48 mmol), HOBT (146 mg, 0.95 mmol) and (R)-quinuclidin-3-ol (181 mg, 1.43 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. The organic layer is dried over Na2SO4, filtered and evaporated to dryness. The crude compound is purified by flash chromatography (DCM/MeOH=95/5) to achieve the title compound as a colorless oil (108 mg, 57% 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 materialThe organic layer is dried over Na2SO4
  6. filtrationfiltered
  7. customevaporated to dryness
  8. customThe crude compound is purified by flash chromatography (DCM/MeOH=95/5)

출처 및 근거

ORD 기록
ord-858f759d6ad748e999ab8b1ab188f5e7
출처 데이터셋
uspto-grants-2014_09
특허 번호
US08835682B2

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