4-Toluenesulfonyl chloride → (2S,4R)-4-(4-Methoxy-benzylsulfanyl)-1-(naphthalene-2-sulfonyl)-pyrrolidine-2-carboxylic acid N'-isobutyl-N'-(4-methyl-benzenesulfonyl)-hydrazide

HRID 1278994Notes

Reaction equation

HRID 1278994 reaction equation
[CH2:1]([NH:5][NH:6][C:7]([C@@H:9]1[CH2:13][C@@H:12]([S:14][CH2:15][C:16]2[CH:21]=[CH:20][C:19]([O:22][CH3:23])=[CH:18][CH:17]=2)[CH2:11][N:10]1[S:24]([C:27]1[CH:36]=[CH:35][C:34]2[C:29](=[CH:30][CH:31]=[CH:32][CH:33]=2)[CH:28]=1)(=[O:26])=[O:25])=[O:8])[CH:2]([CH3:4])[CH3:3].C(N(C(C)C)C(C)C)C.[C:46]1([CH3:56])[CH:51]=[CH:50][C:49]([S:52](Cl)(=[O:54])=[O:53])=[CH:48][CH:47]=1.CNCC(O[K])=O.OS([O-])(=O)=O.[K+]>C(Cl)Cl.CN(C1C=CN=CC=1)C>[CH2:1]([N:5]([S:52]([C:49]1[CH:50]=[CH:51][C:46]([CH3:56])=[CH:47][CH:48]=1)(=[O:54])=[O:53])[NH:6][C:7]([C@@H:9]1[CH2:13][C@@H:12]([S:14][CH2:15][C:16]2[CH:17]=[CH:18][C:19]([O:22][CH3:23])=[CH:20][CH:21]=2)[CH2:11][N:10]1[S:24]([C:27]1[CH:36]=[CH:35][C:34]2[C:29](=[CH:30][CH:31]=[CH:32][CH:33]=2)[CH:28]=1)(=[O:26])=[O:25])=[O:8])[CH:2]([CH3:4])[CH3:3]

Participants

8

Reactant 5

HCID 73974-Toluenesulfonyl chlorideHCID 81531DiisopropylethylamineHCID 516920Potassium bisulfateHCID 69543784(2S,4R)-4-(4-Methoxy-benzylsulfanyl)-1-(naphthalene-2-sulfonyl)-pyrrolidine-2-carboxylic acid N'-isobutyl-hydrazideHCID 178484754HCID 178484754, compound

Product 1

HCID 69543775(2S,4R)-4-(4-Methoxy-benzylsulfanyl)-1-(naphthalene-2-sulfonyl)-pyrrolidine-2-carboxylic acid N'-isobutyl-N'-(4-methyl-benzenesulfonyl)-hydrazideYield 124.8%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

(step 3) 4.3 g (3.15 mmol) (2S,4R)-4-(4-Methoxy-benzylsulfanyl)-1-(naphthalene-2-sulfonyl)-pyrrolidine-2-carboxylic acid N′-isobutyl-hydrazide in 450 ml CH2Cl2 were treated with 5.6 ml (32.6 mmol, 4 eq) N-ethyldiisopropylamine, 3.1 g (16.3 mmol, 2 eq) p-toluene sulfonyl chloride and 100 mg (0.8 mmol, 0.1 eq) DMAP at 0° C. and was stirred at RT over night. 2.05 g (16.1 mmol, 2 eq) MeNHCH2CO2K were added and, the solution was stirred at RT for 1 h, 1M KHSO4 solution was added and, the phases were separated. The organic layer was extracted with sat. NaHCO3 and, the inorganic layers were washed with CH2Cl2. The combined organic phases were washed with brine, dried over Na2SO4 and evaporated. Purification of the crude residue by flash chromatography with hexane:ethyl acetate 2:1 as eluent yields 2.68 g (48%) (2S,4R)-4-(4-Methoxy-benzylsulfanyl)-1-(naphthalene-2-sulfonyl)-pyrrolidine-2-carboxylic acid N′-isobutyl-N′-(4-methyl-benzenesulfonyl)-hydrazide, which was directly subjected to the following reaction.

Workup

  1. stirringthe solution was stirred at RT for 1 h
  2. customthe phases were separated
  3. extractionThe organic layer was extracted with sat. NaHCO3
  4. washthe inorganic layers were washed with CH2Cl2
  5. washThe combined organic phases were washed with brine
  6. dry with materialdried over Na2SO4
  7. customevaporated
  8. customPurification of the crude residue by flash chromatography with hexane:ethyl acetate 2:1 as eluent

Sources & evidence

ORD record
ord-68758f42cef149adab542cf3cf2268ef
Source dataset
uspto-grants-2002_09
Patent number
US06444829B1

Reaction notes

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