4-Methylmorpholine → (E)-2(R)-[1(S)-(tert-butoxycarbonyl)-4-phenyl-3-butenyl]-2'-isobutyl-4-methylvalerohydrazide

HRID 1979187Notes

Reaction equation

HRID 1979187 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]/[CH:10]=[CH:11]/[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].O.O[C:28]1[C:36]2N=[N:34][NH:33][C:32]=2C=CC=1.Cl.[CH2:38](N=C=NCCCN(C)C)C.S(C1C=CC(C)=CC=1)(O)(=O)=O.S(C1C=CC(C)=CC=1)(O)(=O)=O.C(NN)C(C)C.CN1CCOCC1>Cl.C(OC)(C)(C)C>[C:1]([O:5][C:6]([C@H:8]([C@@H:18]([CH2:22][CH:23]([CH3:25])[CH3:24])[C:19]([NH:34][NH:33][CH2:32][CH:36]([CH3:28])[CH3:38])=[O:20])[CH2:9]/[CH:10]=[CH:11]/[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

8

Reactant 5

HCID 79724-MethylmorpholineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 11418712(E)-2(R)-[1(S)-(tert-butoxycarbonyl)-4-phenyl-3-butenyl]-4-methylvaleric acidHCID 21709317Isobutylhydrazine ditosylate saltHCID 178526939HCID 178526939, compound

Product 1

HCID 86756750(E)-2(R)-[1(S)-(tert-butoxycarbonyl)-4-phenyl-3-butenyl]-2'-isobutyl-4-methylvalerohydrazideYield 50.7%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 15413tert-Butyl methyl etherSolvent

Conditions

Temperature
4 °C

Procedure

A solution of 4.05 kg of (E)-2(R)-[1(S)-(tert-butoxycarbonyl)-4-phenyl-3-butenyl]-4-methylvaleric acid in 12 l of dimethylformanide was cooled to 4° C., treated with 1.97 kg of hydroxybenzotriazole hydrate and 2.466 kg of 1-ethyl-3-(3-dimethylaminopropyl)carbodimide hydrochloride and stirred for 2 hours at 4° C. 3.895 kg of isobutylhydrazine ditosylate salt were added followed by 2.36 l of N-methyl-morpholine. The mixture was stirred for 2 hours at 4° C. and for 50 hours at room temperature, diluted with 12 l of 2M hydrochloric acid and 12 l of methyl tert.butyl ether and the organic layer was separated. The organic phase was washed with water, saturated sodium hydrogen carbonate solution and water and then evaporated to give a dark cream colored solid. Recrystallization from hexane gave 2.47 kg of (E)-2(R)-[1(S)-(tert-butoxycarbonyl)-4-phenyl-3-butenyl]-2′-isobutyl-4-methylvalerohydrazide in the form of a cream colored solid.

Workup

  1. stirringThe mixture was stirred for 2 hours at 4° C. and for 50 hours at room temperature
  2. customthe organic layer was separated
  3. washThe organic phase was washed with water, saturated sodium hydrogen carbonate solution and water
  4. customevaporated
  5. customto give a dark cream
  6. customRecrystallization from hexane

Sources & evidence

ORD record
ord-58e34bbb28024f2f91234ba050afef2c
Source dataset
uspto-grants-2001_05
Patent number
US06239151B1

Reaction notes

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