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

HRID 1278992Notes

Reaction equation

HRID 1278992 reaction equation
[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]

Participants

9

Reactant 5

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

Product 1

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

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolvent2×HCID 516892Sodium BicarbonateSolvent

Procedure

(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.

Workup

  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

Sources & evidence

ORD record
ord-179715519f98476895d71a493207828b
Source dataset
uspto-grants-2002_09
Patent number
US06444829B1

Reaction notes

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