4-Methylmorpholine → t-butoxycarbonyl-2,6-dimethyl-D,L-tyrosyl-D-alanine, methyl ester

HRID 745487

Reaction equation

HRID 745487 reaction equation
[C:1]([O:5][C:6]([NH:8][C@H:9]([C:20](O)=[O:21])[CH2:10][C:11]1[C:16]([CH3:17])=[CH:15][C:14]([OH:18])=[CH:13][C:12]=1[CH3:19])=[O:7])([CH3:4])([CH3:3])[CH3:2].CN1CCOCC1.Cl.[CH3:31][O:32][C:33](=[O:37])[C@H:34]([CH3:36])[NH2:35]>C(Cl)Cl>[CH3:2][C:1]([CH3:3])([O:5][C:6]([NH:8][CH:9]([C:20]([NH:35][C@@H:34]([C:33]([O:32][CH3:31])=[O:37])[CH3:36])=[O:21])[CH2:10][C:11]1[C:12]([CH3:19])=[CH:13][C:14]([OH:18])=[CH:15][C:16]=1[CH3:17])=[O:7])[CH3:4]

Participants

5

Reactant 3

HCID 79724-Methylmorpholine2×HCID 2733257Alanine methyl ester hydrochlorideHCID 13656657(S)-2-tert-Butoxycarbonylamino-3-(4-hydroxy-2,6-dimethyl-phenyl)-propionic acid

Product 1

HCID 14620778t-butoxycarbonyl-2,6-dimethyl-D,L-tyrosyl-D-alanine, methyl esterYield 98.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
-30 °C

Procedure

Racemic t-butoxycarbonyl 2,6-dimethyltyrosine (3.9 g, 10 mmoles) was dissolved in 30 ml of CH2Cl2 by adding 1.12 ml (10 mmoles) of NMM. After bringing this mixture to reflux it was cooled to -30° C. and 1.32 ml (10 mmoles) of IBCF were added to this stirred solution. The temperature was allowed to rise to -15° C. and then lowered to -50° C. (D) alanine methyl ester hydrochloride (1.54 g, 11 mmole) was added to the solution followed by 1.3 ml (11 mmoles) of NMM. The mixture was allowed to warm to room temperature and stand for 16 hours. The majority of the CH2Cl2 was removed under reduced pressure. Ethyl acetate (200 ml) was added and this solution was washed twice with 100 ml portions of 0.5 molar KHSO4, once with 100 ml of H2O and dried over MgSO4. Removal of all solvent gave 3.9 g of the mixture of diastereomers. Recrystallization of this material from Skelly B/CH2Cl2 produced 1.6 g (4.2 mmoles) of diastereomer F. Removal of the solvent from the filtrate gave 1.3 g (3.3 mmoles) of diastereomer S contaminated by less than 10% of diastereomer F.

Workup

  1. temperatureto reflux it
  2. addition1.32 ml (10 mmoles) of IBCF were added to this stirred solution
  3. customto rise to -15° C.
  4. customlowered to -50° C.
  5. additionwas added to the solution
  6. temperatureto warm to room temperature
  7. customThe majority of the CH2Cl2 was removed under reduced pressure
  8. additionEthyl acetate (200 ml) was added
  9. washthis solution was washed twice with 100 ml portions of 0.5 molar KHSO4, once with 100 ml of H2O
  10. dry with materialdried over MgSO4
  11. customRemoval of all solvent

Sources & evidence

ORD record
ord-d80ef27fb6844540bbaa235b5b8f22c5
Source dataset
uspto-grants-1986_07
Patent number
US04599325

Linked notes

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