4-Methylmorpholine → HCID 10403069, compound

HRID 1728372Notes

Reaction equation

HRID 1728372 reaction equation
[C:1]1([CH2:7][O:8][C:9]([NH:11][C@@H:12]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:13][C:14]([O-])=[O:15])=[O:10])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.CN1CCOCC1.C(OC(Cl)=O)C>O1CCCC1>[C:1]1([CH2:7][O:8][C:9]([NH:11][C@@H:12]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:13][CH2:14][OH:15])=[O:10])[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1

Participants

5

Reactant 3

HCID 79724-MethylmorpholineHCID 10928Ethyl chloroformateHCID 121592026HCID 121592026, compound

Product 1

HCID 10403069HCID 10403069, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
23 °C

Procedure

29.23 g of N-[(phenylmethoxy)carbonyl]-D-aspartic acid, 1,1-dimethylethyl ester, prepared as in Example C, in 120 mL dry tetrahydrofuran at -10° C. was treated with 10 mL N-methylmorpholine. The mixture was stirred for 3 min and 8.7 mL ethylchloroformate was added dropwise. The mixture was warmed to 23° C. over 15 min and filtered. The filtrate was added dropwise over 30 min to a vigorously stirred mixture of 7.7 g sodium borohydride in 60 mL water at 3° C. The cooling bath was removed, the mixture stirred at 21° C. for 3 h, then cooled to 0° C. and acidified to pH2 with concentrated HCl. The mixture was extracted with 3×200 mL ethyl acetate and the combined organic extracts were washed with brine, dried (Na2SO4) and evaporated to furnish a clear oil. Purification by silica chromatography using methylene chloride-acetone (9:1) as eluent gave the title compound as a clear oil; 21.6 g.

Workup

  1. filtrationfiltered
  2. additionThe filtrate was added dropwise over 30 min to a vigorously stirred mixture of 7.7 g sodium borohydride in 60 mL water at 3° C
  3. customThe cooling bath was removed
  4. stirringthe mixture stirred at 21° C. for 3 h
  5. temperaturecooled to 0° C.
  6. extractionThe mixture was extracted with 3×200 mL ethyl acetate
  7. washthe combined organic extracts were washed with brine
  8. dry with materialdried (Na2SO4)
  9. customevaporated
  10. customto furnish a clear oil
  11. customPurification by silica chromatography

Sources & evidence

ORD record
ord-87ae68ab59824cf28c32b29e3dd9f588
Source dataset
uspto-grants-1994_07
Patent number
US05326760

Reaction notes

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