Methanesulfonyl chloride → 1-[4-Cyano-4-(5-cyano-2-thienyl)-5-methylhexyl]-(3R)-3-tert-butoxycarbonylaminopyrrolidine

HRID 1071641노트

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HRID 1071641 반응식
[C:1]([C:3]([C:11]1[S:12][C:13]([C:16]#[N:17])=[CH:14][CH:15]=1)([CH:8]([CH3:10])[CH3:9])[CH2:4][CH2:5][CH2:6]O)#[N:2].S(Cl)(C)(=O)=O.[I].[Na].[C:25]([O:29][C:30]([NH:32][C@@H:33]1[CH2:37][CH2:36][NH:35][CH2:34]1)=[O:31])([CH3:28])([CH3:27])[CH3:26]>C(#N)C.[Cl-].[Na+].O.C(N(CC)CC)C>[C:1]([C:3]([C:11]1[S:12][C:13]([C:16]#[N:17])=[CH:14][CH:15]=1)([CH:8]([CH3:10])[CH3:9])[CH2:4][CH2:5][CH2:6][N:35]1[CH2:36][CH2:37][C@@H:33]([NH:32][C:30]([O:29][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:31])[CH2:34]1)#[N:2]

참가 물질

8

반응물 4

HCID 31297Methanesulfonyl chlorideHCID 1514397(3R)-(+)-3-(tert-Butoxycarbonylamino)pyrrolidineHCID 223936354-Cyano-4-(5-cyano-2-thienyl)-5-methylhexanolHCID 178506594HCID 178506594, 화합물

생성물 1

HCID 693629501-[4-Cyano-4-(5-cyano-2-thienyl)-5-methylhexyl]-(3R)-3-tert-butoxycarbonylaminopyrrolidine수율 92%

시약·촉매·용매 3

HCID 6342Acetonitrile용매2회HCID 8471Triethylamine용매2회HCID 57417360Sodium chloride; water용매2회

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온도
60 °C

실험 절차

867 mg (3.49 mmol) of 4-cyano-4-(5-cyano-2-thienyl)-5-methylhexanol was dissolved in 20 ml of acetonitrile. 0.58 ml (1.20 eq).of triethylamine and 0.30 ml (1.10 eq) of mesyl chloride were added thereto. After 10 minutes, brine was added, and the objective product was extracted with ethylacetate. The organic layer was washed with brine, and then dried over anhydrous magnesium sulfate. The solvent was evaporated, to give a crude product. The product was dissolved in 30 ml of acetonitrile, 1.57 g (3.00 eq) of sodium iodine, 0.54 ml (1.10 eq) of triethylamine and 845 mg (4.54 mmol) of (3R)-3-tert-butoxycarbonylaminopyrrolidine were added, and the mixture was heated at 60° C. After completion of the reaction, brine was added, and the objective product was extracted with ethyl acetate. The organic layer was washed with brine, and then dried over anhydrous magnesium sulfate. The solvent was evaporated, to give a crude product. The crude product was subjected to 100 g of Cromatorex NH silica gel (ethyl acetate:hexane=25 to 35% of ethyl acetate), to give 1.34 g (3.21 mmol, 92.0%) of the title compound as a yellow oil. The physico-chemical data of the compound was as below.

후처리

  1. extractionthe objective product was extracted with ethylacetate
  2. washThe organic layer was washed with brine
  3. dry with materialdried over anhydrous magnesium sulfate
  4. customThe solvent was evaporated
  5. customto give a crude product
  6. additionwas added
  7. extractionthe objective product was extracted with ethyl acetate
  8. washThe organic layer was washed with brine
  9. dry with materialdried over anhydrous magnesium sulfate
  10. customThe solvent was evaporated
  11. customto give a crude product

출처 및 근거

ORD 기록
ord-056a4df6b1134963a3759c39b4c32a34
출처 데이터셋
uspto-grants-2005_06
특허 번호
US06906072B1

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