N-Methylpiperidine → N1-[2-(4-cyanophenoxy)-1-methylethyl]-N2-phenoxycarbonyl-L-valinamide

HRID 929

반응식

HRID 929 반응식
CN1CCCCC1.[O:8]([C:15]([NH:17][C@H:18]([C:22]([OH:24])=O)[CH:19]([CH3:21])[CH3:20])=[O:16])[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1.ClC(OCC(C)C)=O.[C:33]([C:35]1[CH:45]=[CH:44][C:38]([O:39][CH2:40][CH:41]([NH2:43])[CH3:42])=[CH:37][CH:36]=1)#[N:34]>C(Cl)Cl.O>[C:33]([C:35]1[CH:45]=[CH:44][C:38]([O:39][CH2:40][CH:41]([NH:43][C:22](=[O:24])[C@H:18]([CH:19]([CH3:20])[CH3:21])[NH:17][C:15]([O:8][C:9]2[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=2)=[O:16])[CH3:42])=[CH:37][CH:36]=1)#[N:34]

참가 물질

7

반응물 4

HCID 12291N-MethylpiperidineHCID 62365Isobutyl chloroformateHCID 9816135N-Phenoxycarbonyl-L-valineHCID 189727992-(4-Cyanophenoxy)-1-methylethylamine

생성물 1

HCID 53713420N1-[2-(4-cyanophenoxy)-1-methylethyl]-N2-phenoxycarbonyl-L-valinamide수율 14.4%

시약·촉매·용매 2

HCID 962Water용매HCID 6344Dichloromethane용매

실험 절차

1.8 g of N-methylpiperidine was added to a solution containing 4.2 g of N-phenoxycarbonyl-L-valine dissolved in 100 ml of methylene chloride, at -20° C. After the mixture was stirred for 10 minutes at the same temperature. 2.4 g of isobutyl chloroformate was added to the mixture, and stirred for 1 hour at -20° C. 3.1 g of 2-(4-cyanophenoxy)-1-methylethylamine was added to this mixture at -60° C., and then the reaction mixture was allowed to sit and warm naturally to room temperature while being stirred, and was stirred for 20 hours at room temperature. Water was subsequently added to the reaction mixture. After the methylene chloride layer was washed successively with a 5% aqueous solution of sodium bicarbonate and water, the organic layer was dried over anhydrous magnesium sulfate and the methylene chloride was removed under reduced pressure. The residue was purified by column chromatography on silica gel, thus obtaining 1.0 g of a white powder. 0.6 g of the obtained white powder was purified using high pressure liquid chromatography (hereinafter, referred to as "HPLC") (YMC-063-15, hexane/ethyl acetate=55/45) to separate two fractions. The ingredient of the first fraction possessing a short retention time was 0.3 g of a white powder (yield: 7%) possessing 145 to 147° C. of melting point and the ingredient of the second fraction possessing a long retention time was 0.3 g of a white powder (yield: 7%) possessing a melting point of 166° to 170° C. of melting point.

후처리

  1. stirringstirred for 1 hour at -20° C
  2. stirringwhile being stirred
  3. stirringwas stirred for 20 hours at room temperature
  4. washAfter the methylene chloride layer was washed successively with a 5% aqueous solution of sodium bicarbonate and water
  5. dry with materialthe organic layer was dried over anhydrous magnesium sulfate
  6. customthe methylene chloride was removed under reduced pressure
  7. customThe residue was purified by column chromatography on silica gel

출처 및 근거

ORD 기록
ord-73e9b68ff1584a15b132a29861cc28c2
출처 데이터셋
uspto-grants-1998_03
특허 번호
US05723469

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