Methyl chloroformate → Benzhydryl 7-[2-(1-carbomethoxy-2-propenylamino)-2-phenylacetamido]-3-acetyl-2-cephem-4-carboxylate

HRID 596842Notes

Reaction equation

HRID 596842 reaction equation
[C:1]([CH:5]([NH:8][CH:9]([C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)[C:10]([OH:12])=O)[CH:6]=[CH2:7])([O:3][CH3:4])=[O:2].O1CCCC1.ClC(OC)=O.[NH2:29][CH:30]1[C:56](=[O:57])[N:32]2[CH:33]([C:40]([O:42][CH:43]([C:50]3[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=3)[C:44]3[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=3)=[O:41])[C:34]([C:37](=[O:39])[CH3:38])=[CH:35][S:36][C@H:31]12>CN(CC1C=CC=CC=1)C.C(OCC)(=O)C>[C:1]([CH:5]([NH:8][CH:9]([C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)[C:10]([NH:29][CH:30]1[C:56](=[O:57])[N:32]2[CH:33]([C:40]([O:42][CH:43]([C:50]3[CH:51]=[CH:52][CH:53]=[CH:54][CH:55]=3)[C:44]3[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=3)=[O:41])[C:34]([C:37](=[O:39])[CH3:38])=[CH:35][S:36][C@H:31]12)=[O:12])[CH:6]=[CH2:7])([O:3][CH3:4])=[O:2]

Participants

7

Reactant 4

HCID 6586Methyl chloroformateHCID 8028Tetrahydrofuran2×HCID 211493372-(1-Carbomethoxy-2-propenylamino)-2-phenylacetic acidHCID 131710673Benzhydryl 7-amino-3-acetyl-2-cephem-4-carboxylate

Product 1

HCID 131710676Benzhydryl 7-[2-(1-carbomethoxy-2-propenylamino)-2-phenylacetamido]-3-acetyl-2-cephem-4-carboxylateYield 68%

Reagents, catalysts & solvents 2

HCID 7681N,N-DimethylbenzylamineCatalystHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-15 °C

Procedure

To a cooled (-15° C.), stirred slurry of 0.381 g. of 2-(1-carbomethoxy-2-propenylamino)-2-phenylacetic acid and 25 ml. of tetrahydrofuran was added three drops of N,N-dimethylbenzylamine and 0.109 ml. of methyl chloroformate. The reaction mixture was allowed to stir with cooling under an argon atmosphere for 10 minutes. The reaction mixture was then cooled to -20° C. and a solution of 0.521 g. of benzhydryl 7-amino-3-acetyl-2-cephem-4-carboxylate in 5 ml. of tetrahydrofuran was added dropwise. The resulting mixture was allowed to stir under argon with cooling for approximately one hour, after which time the mixture was transferred to a separatory funnel with the aid of cold ethyl acetate. The organic solution was washed with cold 1N.HCl, and brine, and then dried over anhydrous sodium sulfate. Evaporation in vacuo to dryness gave a product which was chromatographed on silica gel using a toluene-ethyl acetate gradient to give 0.556 g. (68 percent) of the title product as a tan froth:

Workup

  1. stirringto stir
  2. temperaturewith cooling under an argon atmosphere for 10 minutes
  3. temperatureThe reaction mixture was then cooled to -20° C.
  4. stirringto stir under argon
  5. temperaturewith cooling for approximately one hour
  6. washThe organic solution was washed with cold 1N
  7. dry with materialHCl, and brine, and then dried over anhydrous sodium sulfate
  8. customEvaporation in vacuo to dryness
  9. customgave a product which
  10. customwas chromatographed on silica gel using a toluene-ethyl acetate gradient
  11. customto give 0.556 g

Sources & evidence

ORD record
ord-57acdfd99daa4879a510910d515d2d06
Source dataset
uspto-grants-1977_03
Patent number
US04012380

Reaction notes

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