Hydrochloric Acid → (2S)-1-(N-allyloxycarbonyl-N-methylaminoacetyl)-2-(2-methyl-3-oxo-1-butenyl)pyrrolidine

HRID 1650294Notes

Reaction equation

HRID 1650294 reaction equation
P(Cl)(Cl)(Cl)=O.[CH2:6]([O:9][C:10]([N:12]([CH3:17])[CH2:13][C:14]([OH:16])=O)=[O:11])[CH:7]=[CH2:8].C(OC([N:24]1[CH2:28][CH2:27][CH2:26][C@H:25]1[CH:29]=[C:30]([CH3:34])[C:31](=[O:33])[CH3:32])=O)C=C.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CC1(C)CC(=O)CC(=O)C1.Cl>O1CCCC1.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.O.C(OCC)(=O)C.C(O)(=O)C.CN(C)C=O>[CH2:6]([O:9][C:10]([N:12]([CH2:13][C:14]([N:24]1[CH2:28][CH2:27][CH2:26][C@H:25]1[CH:29]=[C:30]([CH3:34])[C:31](=[O:33])[CH3:32])=[O:16])[CH3:17])=[O:11])[CH:7]=[CH2:8]

Participants

13

Reactant 6

HCID 313Hydrochloric AcidHCID 11776TriphenylphosphineHCID 24813Phosphorus oxychlorideHCID 31358DimedoneHCID 19915028N-allyloxycarbonyl-N-methylglycineHCID 57093083(2S)-1-allyloxycarbonyl-2-(2-methyl-3-oxo-1-butenyl)pyrrolidine

Product 1

HCID 57303820(2S)-1-(N-allyloxycarbonyl-N-methylaminoacetyl)-2-(2-methyl-3-oxo-1-butenyl)pyrrolidineYield 26.2%

Reagents, catalysts & solvents 6

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 176Acetic AcidSolventHCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent3×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
5 °C

Procedure

To a mixture of dimethylformamide (4.2 ml) and tetrahydrofuran (10 ml) was added phosphorus oxychloride (4.2 ml) at 5° C. After stirring at 5° C. for 30 minutes, to the mixture were added successively tetrahydrofuran (60 ml) and N-allyloxycarbonyl-N-methylglycine (8.7 g). The mixture was stirred for 30 minutes at 5° C. (solution A). To a solution of (2S)-1-allyloxycarbonyl-2-(2-methyl-3-oxo-1-butenyl)pyrrolidine (10.0 g) in tetrahydrofuran (160 ml) were added successively triphenylphosphine (5.5 g), 5,5-dimethyl-1,3-cyclohexanedione (dimedone) (5.8 g), acetic acid (4.8 ml) and tetrakis(triphenylphosphine)-palladium(0) (2.4 g). After stirring at ambient temperature for 30 minutes, the mixture was taken up into a mixture of ethyl acetate (100 ml) and water (100 ml). After adjusting to around pH 2 with 1N hydrochloric acid, the aqueous layer was separated, washed with e&hyl acetate and tetrahydrofuran (200 ml) was added thereto. After adjusting to around pH 8.5 with 20% aqueous sodium hydroxide, to the mixture was added dropwise the solution A. After stirring at 5° C. for 1 hour, the mixture was extracted with ethyl acetate. The organic layer was washed with water and dried over magnesium sulfate. Removal of the solvent gave a residue, which was chromatographed on silica gel (300 ml) eluting with a mixture of n-hexane and ethyl acetate (5:5-3:7 V/V) to give (2S)-1-(N-allyloxycarbonyl-N-methylaminoacetyl)-2-(2-methyl-3-oxo-1-butenyl)pyrrolidine (3.4 g).

Workup

  1. stirringAfter stirring at ambient temperature for 30 minutes
  2. customthe aqueous layer was separated
  3. washwashed with e&hyl acetate and tetrahydrofuran (200 ml)
  4. additionwas added
  5. additionwas added dropwise the solution A
  6. stirringAfter stirring at 5° C. for 1 hour
  7. extractionthe mixture was extracted with ethyl acetate
  8. washThe organic layer was washed with water
  9. dry with materialdried over magnesium sulfate
  10. customRemoval of the solvent
  11. customgave a residue, which
  12. customwas chromatographed on silica gel (300 ml)
  13. washeluting with a mixture of n-hexane and ethyl acetate (5:5-3:7 V/V)

Sources & evidence

ORD record
ord-99d12d61285040d5b6c32de8b487278f
Source dataset
uspto-grants-1990_05
Patent number
US04923857

Reaction notes

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