Toluene → Methyl N-{[isopropyl(pent-4-en-1-yl)amino]carbonyl}-3-methyl-L-valinate

HRID 1511588Notes

Reaction equation

HRID 1511588 reaction equation
Cl.[CH3:2][O:3][C:4](=[O:11])[C@H:5]([C:7]([CH3:10])([CH3:9])[CH3:8])[NH2:6].[C:12]([O-:15])(O)=O.[Na+].C(Cl)(Cl)=O.C1(C)C=CC=CC=1.[CH:28]([NH:31][CH2:32][CH2:33][CH2:34][CH:35]=[CH2:36])([CH3:30])[CH3:29]>C1COCC1.CCOC(C)=O>[CH:28]([N:31]([CH2:32][CH2:33][CH2:34][CH:35]=[CH2:36])[C:12]([NH:6][C@H:5]([C:4]([O:3][CH3:2])=[O:11])[C:7]([CH3:10])([CH3:9])[CH3:8])=[O:15])([CH3:30])[CH3:29]

Participants

8

Reactant 5

HCID 1140TolueneHCID 6371PhosgeneHCID 516892Sodium BicarbonateHCID 551578Isopropylpent-4-enylamineHCID 16217630Methyl L-tert-leucinate hydrochloride

Product 1

HCID 57692708Methyl N-{[isopropyl(pent-4-en-1-yl)amino]carbonyl}-3-methyl-L-valinate

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution (60 nM) of L-tert-leucine methyl-ester hydrochloride and NaHCO3 (8 eq) in dry THF, a solution 20% w/w of phosgene in toluene (5 eq) was added dropwise at 0° C. and the reaction mixture was stirred at that temperature for 30 minutes. Then the solid was filtered-off and the filtrate evaporated at reduced pressure. The resulting crude yellow oil was taken-up in dry THF (0.3 M) and added dropwise to a stirred solution (0.2 M) of N-isopropylpent-4-en-1-amine and TEA (1 eq). The reaction mixture was stirred at room temperature overnight. Then the mixture was taken-up in EtOAc and washed twice with water and brine. The organic phase was dried over Na2SO4 and the volatiles evaporated at reduced pressure. The crude was purified by flash chromatography eluting with petroleum ether (8) EtOAc (2) using Nynhydrin as stain. Methyl N-{[isopropyl(pent-4-en-1-yl)amino]carbonyl}-3-methyl-L-valinate was obtained as light yellow oil (43%).

Workup

  1. customthe filtrate evaporated at reduced pressure
  2. stirringThe reaction mixture was stirred at room temperature overnight
  3. washwashed twice with water and brine
  4. dry with materialThe organic phase was dried over Na2SO4
  5. customthe volatiles evaporated at reduced pressure
  6. customThe crude was purified by flash chromatography
  7. washeluting with petroleum ether (8) EtOAc (2)

Sources & evidence

ORD record
ord-e7292bffcf374dfe91155e0d3cc2db5c
Source dataset
uspto-grants-2012_07
Patent number
US08216999B2

Reaction notes

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