Acetic Acid → (2S,4R)-4-(4-Methoxy-benzylsulfanyl)-1-(naphthalene-2-sulfonyl)-pyrrolidine-2-carboxylic acid N'-isobutyl-hydrazide

HRID 1278992노트

반응식

HRID 1278992 반응식
[CH3:1][O:2][C:3]1[CH:31]=[CH:30][C:6]([CH2:7][S:8][C@H:9]2[CH2:13][N:12]([S:14]([C:17]3[CH:26]=[CH:25][C:24]4[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=4)[CH:18]=3)(=[O:16])=[O:15])[C@H:11]([C:27]([OH:29])=O)[CH2:10]2)=[CH:5][CH:4]=1.ON1C=CC=CC1=O.[CH2:40]([NH:44][NH2:45])[CH:41]([CH3:43])[CH3:42].S([O-])([O-])(=O)=O.C(O)(=O)C>C(Cl)Cl.O.C([O-])(O)=O.[Na+]>[CH2:40]([NH:44][NH:45][C:27]([C@@H:11]1[CH2:10][C@@H:9]([S:8][CH2:7][C:6]2[CH:5]=[CH:4][C:3]([O:2][CH3:1])=[CH:31][CH:30]=2)[CH2:13][N:12]1[S:14]([C:17]1[CH:26]=[CH:25][C:24]2[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=2)[CH:18]=1)(=[O:16])=[O:15])=[O:29])[CH:41]([CH3:43])[CH3:42]

참가 물질

9

반응물 5

HCID 176Acetic AcidHCID 1117Sulfate IonHCID 69975HydroxypyridinoneHCID 542420IsobutylhydrazineHCID 11442487(2S,4R)-4-(4-Methoxy-benzylsulfanyl)-1-(naphthalene-2-sulfonyl)-pyrrolidine-2-carboxylic acid

생성물 1

HCID 69543784(2S,4R)-4-(4-Methoxy-benzylsulfanyl)-1-(naphthalene-2-sulfonyl)-pyrrolidine-2-carboxylic acid N'-isobutyl-hydrazide수율 99.1%

시약·촉매·용매 3

HCID 962Water용매HCID 6344Dichloromethane용매2회HCID 516892Sodium Bicarbonate용매

실험 절차

(step 1) To a solution of 4.4 g (9.6 mmol) (2S,4R)-4-(4-Methoxy-benzylsulfanyl)-1-(naphthalene-2-sulfonyl)-pyrrolidine-2-carboxylic acid in 200 ml CH2Cl2 were added 1.2 g (10.8 mmol,1.1 eq) N-hydroxy-2-pyridone, followed by 2.2 g (10.7 mmol, 1.1 eq) N, N-dicyclohexylcarbodiimide in 25 ml CH2Cl2 at 0° C. over a period of 30 min. The suspension was stirred for additional 4 h at that temperature before 4.2 ml (33.0 mmol, 3.4 eq) NEM and 1.9 g (mmol, 1.05 eq) isobutylhydrazine.sulfate were added. The reaction mixture was stirred at RT over night. The suspension was treated with 0.55 ml (9.6 mmol, 1.0 eq) glacial acetic acid in 10 ml water and stirred for 1.5 h, diluted with aq. NaHCO3 (5%) and extracted with CH2Cl2. The combined organic phases were washed with 1M KHSO4 solution, water and brine, dried over Na2SO4 and evaporated. Tituration with hexane yields 5.02 g (quant) (2S,4R)-4-(4-Methoxy -benzylsulfanyl)-1-(naphthalene-2-sulfonyl)-pyrrolidine-2-carboxylic acid N′-isobutyl-hydrazide, which was directly subjected to the following reaction.

후처리

  1. stirringstirred for 1.5 h
  2. extractionextracted with CH2Cl2
  3. washThe combined organic phases were washed with 1M KHSO4 solution, water and brine
  4. dry with materialdried over Na2SO4
  5. customevaporated

출처 및 근거

ORD 기록
ord-179715519f98476895d71a493207828b
출처 데이터셋
uspto-grants-2002_09
특허 번호
US06444829B1

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