4-Methylmorpholine → HCID 20281533, compound

HRID 462896Notes

Reaction equation

HRID 462896 reaction equation
[F:1][CH2:2][C:3]([O:5][CH2:6][CH3:7])=[O:4].[H-].[Na+].[N:10]1([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:17][CH2:16][CH2:15][C@H:11]1[C:12](O)=[O:13].CN1CCOCC1.C(OC(Cl)=O)C(C)C>CCOCC.C1COCC1>[CH2:6]([O:5][C:3]([CH:2]([F:1])[C:12]([CH:11]1[CH2:15][CH2:16][CH2:17][N:10]1[C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])=[O:13])=[O:4])[CH3:7]

Participants

8

Reactant 5

HCID 79724-MethylmorpholineHCID 9988Ethyl fluoroacetateHCID 24758Sodium hydrideHCID 62365Isobutyl chloroformateHCID 850831,2-Pyrrolidinedicarboxylic acid, 1-(1,1-dimethylethyl) ester, (2S)-2×

Product 1

HCID 20281533HCID 20281533, compound

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

Ethyl fluoroacetate (2.0 g, 18.9 m mol) in ether (25 ml) was added dropwise with stirring to a suspension of NaH (50 percent oil dispersion)(0.91 g, 18.9 m mol) in ether (20 ml). The reaction mixture was stirred three hours at room temperature, then cooled to -15°. The mixed anhydride of Boc-Pro-OH [prepared from Boc-Pro-OH (4.1 g, 18.9 m mol) in the THF (50 ml) containing N-methylmorpholine (2.1 ml, 18.9 m mol) at -15°, by the addition of isobutylchloroformate (2.45 ml, 18.9 m mol) and stirred 5 minutes] was filtered into the chilled enolate suspension and stirred at -15° for 10 minutes. The reaction was then allowed to warm to room temperature for one hour. The solution was poured onto ice containing 2.5N H2SO4. The organic solvents were removed by evaporation and the aqueous residue extracted with ethyl acetate. The ethyl acetate solution was washed with saturated NaHCO3, saturated with NaCl, and dried over anhydrous MgSO4. The ethyl acetate was removed by evaporation and the residue was applied to a silica gel column. The product was eluted with chloroform. The solvent was removed by evaporation yielding 1.08 g of an oil. The 1H nmr (CDCl3) showed peaks shifted from TMS by ##STR5##

Workup

  1. temperaturecooled to -15°
  2. stirringstirred 5 minutes]
  3. filtrationwas filtered into the chilled enolate suspension
  4. stirringstirred at -15° for 10 minutes
  5. temperatureto warm to room temperature for one hour
  6. additionThe solution was poured onto ice containing 2.5N H2SO4
  7. customThe organic solvents were removed by evaporation
  8. extractionthe aqueous residue extracted with ethyl acetate
  9. washThe ethyl acetate solution was washed with saturated NaHCO3, saturated with NaCl
  10. dry with materialdried over anhydrous MgSO4
  11. customThe ethyl acetate was removed by evaporation
  12. washThe product was eluted with chloroform
  13. customThe solvent was removed by evaporation

Sources & evidence

ORD record
ord-070aed6636b246199e21746f620cbac5
Source dataset
uspto-grants-1985_05
Patent number
US04518528

Reaction notes

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