4-Methylmorpholine → HCID 14208549, compound

HRID 845326Notes

Reaction equation

HRID 845326 reaction equation
[C:1]([NH:8][C@H:9]([C:18]([OH:20])=O)[CH2:10][C:11]1[CH:16]=[CH:15][C:14]([OH:17])=[CH:13][CH:12]=1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].CN1CCOCC1.C(OC(Cl)=O)C(C)C.Cl.[CH3:37][O:38][C:39](=[O:46])[C@@H:40]([CH2:42][CH2:43][S:44][CH3:45])[NH2:41]>C(Cl)Cl>[CH3:7][C:4]([CH3:5])([O:3][C:1]([NH:8][C@H:9]([C:18]([NH:41][C@@H:40]([C:39]([O:38][CH3:37])=[O:46])[CH2:42][CH2:43][S:44][CH3:45])=[O:20])[CH2:10][C:11]1[CH:12]=[CH:13][C:14]([OH:17])=[CH:15][CH:16]=1)=[O:2])[CH3:6]

Participants

6

Reactant 4

HCID 79724-Methylmorpholine2×HCID 62365Isobutyl chloroformateHCID 117439L-Tyrosine, N-(1,1-dimethylethoxy)carbonyl-HCID 12888616Methyl D-methioninate--hydrogen chloride (1/1)

Product 1

HCID 14208549HCID 14208549, compoundYield 98.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
-78 °C

Procedure

To Boc-tyrosine (16.9 g, 60 mmol) in 150 ml of methylene chloride (CH2Cl2) cooled to 0° C. under an argon (Ar) atmosphere were added 6.6 ml (60 mmol) of N-methylmorpholine (NMM). After cooling this vigorously stirred solution to -78° C., 7.9 ml (60 mmol) of isobutylchloroformate (IBCF) were added to this reaction. The mixture was allowed to warm to 20° C. before it was again cooled to -78° and another 7.9 ml (60 mmol) of NMM were added. (D)Methionine methyl ester hydrochloride (12.0 g, 60 mmol) was then added to the reaction in a single portion. The mixture was allowed to warm to room temperature and stir for an additional 18 hours (h). After filtering the reaction through diatomaceous earth, the filtrate was washed 3×100 ml 0.5N potassium bisulfate (KHSO4). The combined aqueous washed was extracted with CH2Cl2 (100 ml). The combined organic extracts were washed with 100 ml of brine, dried over sodium sulfate (Na2SO4) and stripped of all solvent under reduced pressure to produce the title product (25.1 g) as a light yellow glass. The material was used in subsequent reactions without further purification.

Workup

  1. temperatureto warm to 20° C. before it
  2. temperaturewas again cooled to -78°
  3. temperatureto warm to room temperature
  4. filtrationAfter filtering
  5. customthe reaction through diatomaceous earth
  6. washthe filtrate was washed 3×100 ml 0.5N potassium bisulfate (KHSO4)
  7. washThe combined aqueous washed
  8. extractionwas extracted with CH2Cl2 (100 ml)
  9. washThe combined organic extracts were washed with 100 ml of brine
  10. dry with materialdried over sodium sulfate (Na2SO4)

Sources & evidence

ORD record
ord-c0dd686ac70a47949ff3fa9fd13b5901
Source dataset
uspto-grants-1988_07
Patent number
US04757153

Reaction notes

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