4-Methylmorpholine → t-Butoxycarbonylvalyltyrosine methyl ester

HRID 1395809Notes

Reaction equation

HRID 1395809 reaction equation
[C:1]([O:5][C:6]([NH:8][C@H:9]([C:13]([OH:15])=O)[CH:10]([CH3:12])[CH3:11])=[O:7])([CH3:4])([CH3:3])[CH3:2].CN1CCOCC1.C(OC(Cl)=O)C(C)C.Cl.[CH3:32][O:33][C:34](=[O:45])[C@H:35]([CH2:37][C:38]1[CH:43]=[CH:42][C:41]([OH:44])=[CH:40][CH:39]=1)[NH2:36]>C(Cl)Cl>[CH3:32][O:33][C:34](=[O:45])[C@H:35]([CH2:37][C:38]1[CH:39]=[CH:40][C:41]([OH:44])=[CH:42][CH:43]=1)[NH:36][C:13](=[O:15])[C@H:9]([CH:10]([CH3:11])[CH3:12])[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 76956Methyl tyrosinate hydrochlorideHCID 83693Boc-L-Valine

Product 1

HCID 14752398t-Butoxycarbonylvalyltyrosine methyl ester

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
-70 °C

Procedure

21.7 g of t-butoxycarbonylvaline is dissolved in 200 ml of methylene chloride. 22.2 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 again cooled to -70° C. 23.2 g of tyrosine methyl ester hydrochloride 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 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-butoxycarbonylvalyltyrosine methyl ester.

Workup

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

Sources & evidence

ORD record
ord-2273e8eb9ebd41a58e68eaeaf23ea4ac
Source dataset
uspto-grants-1980_05
Patent number
US04204991

Reaction notes

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