N,N-Dimethylaniline → 2,2,2-Trichloroethyl 2-methyl-2,3-methylene-6-[2-(2-thienyl)acetamido]penam-3-carboxylate

HRID 1287323Notes

Reaction equation

HRID 1287323 reaction equation
[CH3:1][C:2]12[CH2:15][C:6]1([C:7]([O:9][CH2:10][C:11]([Cl:14])([Cl:13])[Cl:12])=[O:8])[N:5]1[C:16](=[O:28])[CH:17]([NH:18][C:19](=[O:27])[CH2:20][C:21]3C=C[CH:24]=[CH:23][CH:22]=3)[C@H:4]1[S:3]2.P(Cl)(Cl)(Cl)(Cl)Cl.CN(C)C1C=CC=CC=1.[S:44]1C=CC=C1CC(Cl)=O>C1C=CC=CC=1.CO.N1C=CC=CC=1>[CH3:1][C:2]12[CH2:15][C:6]1([C:7]([O:9][CH2:10][C:11]([Cl:13])([Cl:12])[Cl:14])=[O:8])[N:5]1[C:16](=[O:28])[CH:17]([NH:18][C:19](=[O:27])[CH2:20][C:21]3[S:44][CH:24]=[CH:23][CH:22]=3)[C@H:4]1[S:3]2

Participants

8

Reactant 4

HCID 949N,N-DimethylanilineHCID 24819Phosphorus pentachlorideHCID 1623622-Thiopheneacetyl chlorideHCID 128339582,2,2-Trichloroethyl 2-methyl-2,3-methylene-6-(2-phenylacetamido)penam-3-carboxylate

Product 1

HCID 155823632,2,2-Trichloroethyl 2-methyl-2,3-methylene-6-[2-(2-thienyl)acetamido]penam-3-carboxylateYield 8.6%

Reagents, catalysts & solvents 3

HCID 241BenzeneSolvent2×HCID 887MethanolSolventHCID 1049PyridineSolvent

Conditions

Temperature
10 °C

Procedure

To a solution of 2,2,2-trichloroethyl 2-methyl-2,3-methylene-6-(2-phenylacetamido)penam-3-carboxylate (1.2 g.) in benzene (30 ml.) were added pyridine (0.36 g.) and phosphorus pentachloride (0.9 g.) under stirring and cooling at 10°C, and the mixture was stirred for 2 hours at room temperature. The solution was cooled at 10°C and absolute methanol (3 ml.) was added to the solution, after which the mixture was stirred for 2 hours at room temperature. Dimethylaniline (2.35 g.) and a solution of (2-thienyl)acetyl chloride (0.42 g.) in anhydrous benzene (5 ml.) were dropwise added to the solution under stirring and cooling at -5°C, and the mixture was stirred for 30 minutes at the same temperature and 1.5 hours at room temperature. The reaction mixture was washed with 5% hydrochloric acid, water, 5% sodium bicarbonate aqueous solution and water in turn and then dried. After drying, the solvent was removed and the residue oil was purified by column chromatography on silica gel (20 g.) using chloroform as developing solvent. The eluate was separated into each 50 ml. fraction and the 12th to 14th fractions were concentrated. The residue was crystallized from ether to give crystals of 2,2,2-trichloroethyl 2-methyl-2,3-methylene-6-[2-(2-thienyl)acetamido]penam-3-carboxylate (105 mg.), mp 144° to 145°C (dec.).

Workup

  1. stirringthe mixture was stirred for 2 hours at room temperature
  2. temperatureThe solution was cooled at 10°C
  3. stirringafter which the mixture was stirred for 2 hours at room temperature
  4. stirringunder stirring
  5. temperaturecooling at -5°C
  6. stirringthe mixture was stirred for 30 minutes at the same temperature and 1.5 hours at room temperature
  7. washThe reaction mixture was washed with 5% hydrochloric acid, water, 5% sodium bicarbonate aqueous solution and water in turn
  8. customdried
  9. customAfter drying
  10. customthe solvent was removed
  11. customthe residue oil was purified by column chromatography on silica gel (20 g.)
  12. customThe eluate was separated into each 50 ml
  13. concentrationfraction and the 12th to 14th fractions were concentrated
  14. customThe residue was crystallized from ether

Sources & evidence

ORD record
ord-cbbe02ab272b48ce9ef14f1b70494e58
Source dataset
uspto-grants-1976_10
Patent number
US03984397

Reaction notes

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