4-Methylmorpholine → HCID 22880227, compound

HRID 726991Notes

Reaction equation

HRID 726991 reaction equation
[Cl:1][CH2:2][C:3]([NH:5][C:6]1[CH:11]=[CH:10][C:9](/[CH:12]=[CH:13]/[C:14]([OH:16])=O)=[CH:8][CH:7]=1)=[O:4].CN1CCOCC1.ClC(OCC(C)C)=O.[C@@H:32]12[C:38](=[O:39])[NH:37][C@@H:36]1[CH2:35][CH2:34][NH:33]2>O1CCCC1.ClCCl.CN(C)C=O>[Cl:1][CH2:2][C:3]([NH:5][C:6]1[CH:7]=[CH:8][C:9](/[CH:12]=[CH:13]/[C:14](=[O:16])[N:33]2[CH2:34][CH2:35][C@@H:36]3[C@H:32]2[C:38](=[O:39])[NH:37]3)=[CH:10][CH:11]=1)=[O:4]

Participants

8

Reactant 4

HCID 79724-MethylmorpholineHCID 62365Isobutyl chloroformateHCID 10820492(1S,5R)-2,6-Diazabicyclo[3.2.0]heptan-7-oneHCID 18523124HCID 18523124, compound

Product 1

HCID 22880227HCID 22880227, compound

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-10 °C

Procedure

(E)-3-(4-Chloroacetylaminophenyl)acrylic acid (1.44 g, 6.0 mmol) was suspended in 50 ml of tetrahydrofuran, treated with 0.66 ml (6.0 mmol) of N-methylmorpholine and cooled to -10° C. Subsequently, 0.8 ml (6.0 mmol) of isobutyl chloroformate was added dropwise thereto, the mixture was stirred for 30 minutes while cooling and then, at room temperature overnight. The solvent was removed in a vacuum, the residue was taken up in ethyl acetate and extracted twice with water and once with saturated aqueous sodium chloride solution. The organic phase was dried over magnesium sulphate and concentrated. The thus-obtained mixed anhydride was diluted in 25 ml of dichloromethane and added dropwise to a solution of 500 mg (4.5 mmol) of (1S,5R)-2,6-diazabicyclo[3.2.0]heptan-7-one (Example 2) dissolved in 25 ml of dichloromethane and 4 ml of dimethylformamide. The mixture was left to react overnight and the product which separates was filtered off under suction. The latter was purified by chromatography (silica gel, 1. ethyl acetate, 2. ethyl acetate/ethanol=3:2). Yield: 1.0 g (50%).

Workup

  1. temperaturewhile cooling
  2. customat room temperature
  3. customovernight
  4. customThe solvent was removed in a vacuum
  5. extractionextracted twice with water and once with saturated aqueous sodium chloride solution
  6. dry with materialThe organic phase was dried over magnesium sulphate
  7. concentrationconcentrated
  8. additionThe thus-obtained mixed anhydride
  9. additionwas diluted in 25 ml of dichloromethane
  10. waitThe mixture was left
  11. customto react overnight
  12. filtrationthe product which separates was filtered off under suction
  13. customThe latter was purified by chromatography (silica gel, 1. ethyl acetate, 2. ethyl acetate/ethanol=3:2)

Sources & evidence

ORD record
ord-99ecce322eb64c2aacb83a0e633e0c27
Source dataset
uspto-grants-1998_01
Patent number
US05712268

Reaction notes

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