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

HRID 1386559Notes

Reaction equation

HRID 1386559 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>CN(C)C=O.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

9

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 3

HCID 313Hydrochloric AcidSolventHCID 6228DimethylformamideSolventHCID 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 dimethylformamide was cooled to 4° C. and treated with 1.97 kg of hydroxybenzotriazole hydrate and 2.466 kg of 1-ethyl-3-(3-dimethylaminopropyl)carbodimide hydrochloride and the solution was stirred for 2 hours at 4° C. 3.895 kg of isobutylhydrazine di-tosylate salt were added followed by 2.36 1 of N-methylmorpholine 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 phase was separated. The organic phase was washed with water, saturated sodium hydrogen carbonate solution and water and then evaporated to give a dark cream solid. Recrystallization from hexane gave 2.47 kg of (E)-2(R)-[1 (S)-(tert-butoxycarbonyl)-4-phenyl-3-butenyl]-2′-isobutyl-4-methyl-valerohydrazide in the form of a cream solid.

Workup

  1. stirringwas stirred for 2 hours at 4° C. and for 50 hours at room temperature
  2. customthe organic phase 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 solid
  6. customRecrystallization from hexane

Sources & evidence

ORD record
ord-a90be23ec4e44177b30a228cfcb5fdb6
Source dataset
uspto-grants-2001_07
Patent number
US06265446B1

Reaction notes

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