4-Methylmorpholine → HCID 56639216, compound

HRID 1981407Notes

Reaction equation

HRID 1981407 reaction equation
[CH3:1][C:2]([CH3:13])([O:4][C:5]([NH:7][C@H:8]([C:10]([OH:12])=O)[CH3:9])=[O:6])[CH3:3].CN1CCOCC1.ClC(OCC(C)C)=O.[N+:29](=[CH2:31])=[N-:30]>O1CCCC1.CCOCC>[N+:29](=[CH:31][C:10](=[O:12])[C@@H:8]([NH:7][C:5](=[O:6])[O:4][C:2]([CH3:1])([CH3:3])[CH3:13])[CH3:9])=[N-:30]

Participants

7

Reactant 4

HCID 79724-MethylmorpholineHCID 9550DiazomethaneHCID 62365Isobutyl chloroformateHCID 85082Tert-butoxycarbonylalanine

Product 1

HCID 56639216HCID 56639216, compound

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

To a vigorously stirred solution of N-[(1,1-dimethylethoxy)carbonyl]-L-alanine (15.14 g., 80 mmole) and N-methylmorpholine (8.80 ml., 80 mmole) in dry tetrahydrofuran (80 ml.) at -15° under argon is added a solution of isobutyl chloroformate (10.37 ml., 80 mmole) in tetrahydrofuran (10 ml.) while maintaining the reaction temperature below -12°. After the addition is complete, the reaction mixture is stirred for 14 minutes, diluted with anhydrous ether (250 ml., prechilled to -20°), and quickly filtered. Approximately one-fourth of the filtrate is transferred to a separatory funnel (the remainder is kept chilled) and added rapidly to a gently stirred, chilled (0°) solution of diazomethane (160 mmole). Additional chilled portions are transferred to the separatory funnel until the entire solution has been added (approximately 10 minutes). The resulting solution is stirred for 2 hours, warming gently to room temperature, then purged with nitrogen for 1 hour, washed with chilled half-saturated sodium bicarbonate (2×100 ml.) and water (3×50 ml.), dried (Na2SO4), and evaporated to a yellow semi-crystalline residue. Two recrystallizations from ethyl acetate-petroleum ether yield 10.29 g. of product as yellow plates; m.p. 99°-102° plus an additional crop of 1.33 g.; m.p. 97.5°-101°. A portion is recrystallized once more giving an analytically pure sample of (S)-(3-diazo-1-methyl-2-oxopropyl)carbamic acid, 1,1-dimethylethyl ester; m.p. 102°-103°.

Workup

  1. temperaturewhile maintaining the reaction temperature below -12°
  2. additionAfter the addition
  3. filtrationquickly filtered
  4. customApproximately one-fourth of the filtrate is transferred to a separatory funnel
  5. temperature(the remainder is kept chilled) and
  6. additionadded rapidly to
  7. stirringa gently stirred
  8. temperatureAdditional chilled portions
  9. additionhas been added (approximately 10 minutes)
  10. stirringThe resulting solution is stirred for 2 hours
  11. custompurged with nitrogen for 1 hour
  12. washwashed with chilled half-saturated sodium bicarbonate (2×100 ml.) and water (3×50 ml.)
  13. dry with materialdried (Na2SO4)
  14. customevaporated to a yellow semi-crystalline residue
  15. customTwo recrystallizations from ethyl acetate-petroleum ether yield 10.29 g
  16. customA portion is recrystallized once more

Sources & evidence

ORD record
ord-49578b02701e4b1a9bbdd8885a888266
Source dataset
uspto-grants-1985_04
Patent number
US04514391

Reaction notes

Loading…