4-Methylmorpholine → 2(R)-[1(S)-(tert-butoxycarbonyl)-4-phenylbutyl]-4-methylvalerohydrazide

HRID 651803Notes

Reaction equation

HRID 651803 reaction equation
[C:1]([O:5][C:6]([C@H:8]([C@@H:18]([CH2:22][CH:23]([CH3:25])[CH3:24])[C:19](O)=[O:20])[CH2:9][CH2:10][CH2:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].FC1C(O)=C(F)C(F)=C(F)C=1F.Cl.C(N=C=NCCCN(C)C)C.Cl.[NH2:51][NH2:52].CN1CCOCC1>CN(C)C=O>[C:1]([O:5][C:6]([C@H:8]([C@@H:18]([CH2:22][CH:23]([CH3:25])[CH3:24])[C:19]([NH:51][NH2:52])=[O:20])[CH2:9][CH2:10][CH2:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 5

HCID 79724-MethylmorpholineHCID 13041PentafluorophenolHCID 115031Hydrazinium chlorideHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 153807642(R)-[1(S)-(tert-butoxycarbonyl)-4-phenylbutyl]-4-methylvaleric acid

Product 1

HCID 702001082(R)-[1(S)-(tert-butoxycarbonyl)-4-phenylbutyl]-4-methylvalerohydrazideYield 43.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

A solution of 4.8 g of 2(R)-[1(S)-(tert-butoxycarbonyl)-4-phenylbutyl]-4-methylvaleric acid in 50 ml of dimethylformamide was cooled to 0° C. and treated with 2.80 g of pentafluorophenol and 2.65 g of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride. The mixture was stirred at 0° C. for 2.5 hours and then treated with 4.73 g of hydrazine monohydrochloride and 6.97 g of 4-methyl morpholine. The mixture was stirred for a further 18 hours at room temperature and then evaporated. The residue was dissolved in ethyl acetate and washed sequentially with 2M aqueous hydrogen chloride, 5% aqueous sodium hydrogen carbonate, water, and saturated aqueous sodium chloride. The organic layer was dried over anhydrous magnesium sulphate and evaporated. The residue was purified by flash column chromatography on silica gel using ethyl acetate/hexane (1:1) as the eluant to give 2.18 g of 2(R)-[1(S)-(tert-butoxycarbonyl)-4-phenylbutyl]-4-methylvalerohydrazide in the form of a pale yellow solid.

Workup

  1. stirringThe mixture was stirred for a further 18 hours at room temperature
  2. customevaporated
  3. dissolutionThe residue was dissolved in ethyl acetate
  4. washwashed sequentially with 2M aqueous hydrogen chloride, 5% aqueous sodium hydrogen carbonate, water, and saturated aqueous sodium chloride
  5. dry with materialThe organic layer was dried over anhydrous magnesium sulphate
  6. customevaporated
  7. customThe residue was purified by flash column chromatography on silica gel

Sources & evidence

ORD record
ord-bc8b8e844f9b4205a51ec77fdbad6a80
Source dataset
uspto-grants-2001_08
Patent number
US06281363B1

Reaction notes

Loading…