4-Methylmorpholine → HCID 178455968, compound

HRID 1395816Notes

Reaction equation

HRID 1395816 reaction equation
[C:1]([O:5][C:6]([NH:8][C@H:9]([C:14]([OH:16])=O)[C@H:10]([CH2:12][CH3:13])[CH3:11])=[O:7])([CH3:4])([CH3:3])[CH3:2].CN1CCOCC1.C(OC(Cl)=O)C(C)C.Cl.Cl.[CH3:34][O:35][C:36](=[O:45])[C@H:37]([CH2:39][C:40]1[N:44]=[CH:43][NH:42][CH:41]=1)[NH2:38]>C(Cl)Cl>[CH3:34][O:35][C:36](=[O:45])[C@H:37]([CH2:39][C:40]1[N:44]=[CH:43][NH:42][CH:41]=1)[NH:38][C:14](=[O:16])[C@H:9]([C@H:10]([CH2:12][CH3:13])[CH3:11])[NH:8][C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7]

Participants

6

Reactant 4

HCID 79724-MethylmorpholineHCID 62365Isobutyl chloroformateHCID 2724762tert-Butoxycarbonyl-L-isoleucineHCID 178419105HCID 178419105, compound

Product 1

HCID 178455968HCID 178455968, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
-70 °C

Procedure

23.3 of t-butoxycarbonylisoleucine is dissolved in 200 ml of methylene chloride. 33.3 ml of N-methylmorpholine is added to the solution. The solution is cooled to -70° C. 13.1 ml of isobutylchloroformate is then added. The reaction mixture is warmed up to -15° C. and stirred for 5 minutes. The reaction mixture is again cooled to -70° C. 26.0 g of histidine methyl ester dihydrochloride is added to the reaction mixture. The reaction mixture is allowed to warm to room temperature, and then is stirred for 16 hours. The reaction mixture is extracted three times with 0.5 M potassium bisulfate and once with brine. The methylene chloride solution is dried over anhydrous sodium sulfate, filtered and stripped of of solvent. The residue is dissolved in 200 ml of ethyl ether. The ether solution is added to cold rapidly stirring Skellysolve B. The white precipitate is filtered and dried to afford the product t-butoxycarbonylisoleucylhistidine methyl ester.

Workup

  1. temperatureThe reaction mixture is warmed up to -15° C.
  2. temperatureThe reaction mixture is again cooled to -70° C
  3. temperatureto warm to room temperature
  4. stirringis stirred for 16 hours
  5. extractionThe reaction mixture is extracted three times with 0.5 M potassium bisulfate
  6. dry with materialThe methylene chloride solution is dried over anhydrous sodium sulfate
  7. filtrationfiltered
  8. dissolutionThe residue is dissolved in 200 ml of ethyl ether
  9. additionThe ether solution is added to cold rapidly stirring Skellysolve B
  10. filtrationThe white precipitate is filtered
  11. customdried

Sources & evidence

ORD record
ord-c61da95c40834ea890e642dd00272090
Source dataset
uspto-grants-1980_05
Patent number
US04204991

Reaction notes

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