4-Methylmorpholine → HCID 69531264, compound

HRID 1357464Notes

Reaction equation

HRID 1357464 reaction equation
C1([NH3+])CCCCC1.[CH2:8]([O:10][C:11]([NH:13][C@H:14]([C:23]([O-:25])=O)[CH2:15][C:16]1[CH:21]=[CH:20][C:19]([OH:22])=[CH:18][CH:17]=1)=[O:12])[CH3:9].CN1CCOCC1.C(O)(=O)C(O)=O.[NH2:39][C@H:40]([C:45]([NH:47][C@H:48]([C:50]([O:52][CH3:53])=[O:51])[CH3:49])=[O:46])[C@H:41]([CH2:43][CH3:44])[CH3:42].C(N(CC)CC)C>C(OCC)(=O)C.OS([O-])(=O)=O.[K+].CN(C)C=O>[CH2:8]([O:10][C:11]([NH:13][C@H:14]([C:23]([NH:39][C@H:40]([C:45]([NH:47][C@H:48]([C:50]([O:52][CH3:53])=[O:51])[CH3:49])=[O:46])[C@H:41]([CH2:43][CH3:44])[CH3:42])=[O:25])[CH2:15][C:16]1[CH:17]=[CH:18][C:19]([OH:22])=[CH:20][CH:21]=1)=[O:12])[CH3:9]

Participants

8

Reactant 4

HCID 79724-MethylmorpholineHCID 8471TriethylamineHCID 87877525HCID 87877525, compoundHCID 131723970HCID 131723970, compound

Product 1

HCID 69531264HCID 69531264, compound

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolventHCID 516920Potassium bisulfateSolvent

Conditions

Temperature
-15 °C

Procedure

1.8 g (5 mmol) of ethoxycarbonyl-L-tyrosine cyclohexyl-ammonium salt (Example 3, Step A2) are dissolved in 20 ml of ethyl acetate and 6 ml of 1 M KHSO4. The phases are separated, the ethyl acetate phase is washed neutral with water, dried over anhydrous sodium sulfate and evaporated at a pressure of 2.0-2.5 kPa. The residue is dissolved in 5 ml of dimethylformamide, chilled to −15° C. and under constant stirring 0.55 ml (5 mmol) of N-methyl-morpholine and 0.66 ml of isobutyl chlorofomnnate are added. After 10 min. the following solution chilled to −15° C. is added: 1.5 g (5 mmol) of methyl L-isoleucyl-L-alaninate oxalate (Example 3, Step A4) and 1.4 ml (10 mmol) of triethylamine in 5 ml of dimethylformamide. The reaction mixture is stirred under cooling for 30 min, then at room temperature for further 30 min, then it is filtered and evaporated at a pressure of 2.0-2.5 kPa. The residue is dissolved in 30 ml of ethyl acetate, washed with 2×10 ml of 1 M KHSO4 and 2×10 ml of water, and evaporated at 2.0-2.5 kPa. The residue is crystallyzed with diethyl ether, filtered, washed with diethyl ether and dried in a vacuum desiccator.

Workup

  1. customThe phases are separated
  2. washthe ethyl acetate phase is washed neutral with water
  3. dry with materialdried over anhydrous sodium sulfate
  4. customevaporated at a pressure of 2.0-2.5 kPa
  5. dissolutionThe residue is dissolved in 5 ml of dimethylformamide
  6. additionare added
  7. temperatureAfter 10 min. the following solution chilled to −15° C.
  8. additionis added
  9. temperatureunder cooling for 30 min
  10. filtrationit is filtered
  11. customevaporated at a pressure of 2.0-2.5 kPa
  12. dissolutionThe residue is dissolved in 30 ml of ethyl acetate
  13. washwashed with 2×10 ml of 1 M KHSO4 and 2×10 ml of water
  14. customevaporated at 2.0-2.5 kPa
  15. filtrationfiltered
  16. washwashed with diethyl ether
  17. customdried in a vacuum desiccator

Sources & evidence

ORD record
ord-bda6032b98a947758915f71865b2e970
Source dataset
uspto-grants-2003_07
Patent number
US06593300B1

Reaction notes

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