4-Methylmorpholine → HCID 13685960, compound

HRID 1980755Notes

Reaction equation

HRID 1980755 reaction equation
[C:1]([N:11]1[CH2:18][CH2:17][CH2:16][C@H:12]1[C:13]([OH:15])=O)([O:3][CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)=[O:2].CN1CCOCC1.ClC(OCC(C)C)=O.[NH2:34][C@H:35]([CH2:40][OH:41])[CH2:36][CH:37]([CH3:39])[CH3:38]>O1CCCC1.CC(C)=O>[C:1]([N:11]1[CH2:18][CH2:17][CH2:16][C@H:12]1[C:13]([NH:34][C@H:35]([CH2:40][OH:41])[CH2:36][CH:37]([CH3:39])[CH3:38])=[O:15])([O:3][CH2:4][C:5]1[CH:6]=[CH:7][CH:8]=[CH:9][CH:10]=1)=[O:2]

Participants

7

Reactant 4

HCID 79724-MethylmorpholineHCID 62365Isobutyl chloroformateHCID 101987Benzyloxycarbonyl-L-prolineHCID 111307L-Leucinol

Product 1

HCID 13685960HCID 13685960, compoundYield 58%

Reagents, catalysts & solvents 2

HCID 180AcetoneSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

A solution containing 2.49 g (10 mmol) N-carbobenzoxy-L-proline and 1.01 g (10 mmol) N-methylmorpholine in approximately 100 ml tetrahydrofuran (THF) was cooled to -20° under nitrogen, and 1.37 g (10 mmol) isobutyl chloroformate was added with magnetic stirring. After five minutes, a solution of 1.17 g (10 mmol) L-leucinol in 5 mL THF was added, and the resulting reaction mixture was stirred for 30 minutes at 0°. THF evaporated under vacuum, and 30 mL water and 100 mL ethyl acetate were added to the resulting residue. After separation of aqueous and organic layers, the organic layer was decanted and retained. The aqueous layer was extracted with a second aliquot (100 mL) of ethyl acetate, and the resulting organic phase was separated. The combined organic layers were washed with 50 mL of ice-cold, 5% aqueous citric acid, followed by 50 mL of an ice-cold, 5% sodium bicarbonate solution. An organic phase was separated, dried over anhydrous magnesium sulfate, and the ethyl acetate was evaporated to provide 3.25 g of crude product. Recrystallization from a mixture of 40 mL ethyl acetate and 25 mL n-hexane gave 2.03 g (5.8 mmol; 58%) of colorless N-carbobenzoxy-L-prolyl-L-leucinol, m.p. 95°-95.5°, α25D-72°, (C=1.03 g/100 mL acetone).

Workup

  1. temperaturewas cooled to -20° under nitrogen
  2. customthe resulting reaction mixture
  3. customTHF evaporated under vacuum, and 30 mL water and 100 mL ethyl acetate
  4. additionwere added to the resulting residue
  5. customAfter separation of aqueous and organic layers
  6. customthe organic layer was decanted
  7. extractionThe aqueous layer was extracted with a second aliquot (100 mL) of ethyl acetate
  8. customthe resulting organic phase was separated
  9. washThe combined organic layers were washed with 50 mL of ice-cold, 5% aqueous citric acid
  10. customAn organic phase was separated
  11. dry with materialdried over anhydrous magnesium sulfate
  12. customthe ethyl acetate was evaporated
  13. customto provide 3.25 g of crude product
  14. customRecrystallization
  15. additionfrom a mixture of 40 mL ethyl acetate and 25 mL n-hexane

Sources & evidence

ORD record
ord-c6191ba4d9fe48ffae96c51cb40e9e1e
Source dataset
uspto-grants-1985_04
Patent number
US04511390

Reaction notes

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