Cephalothin → HCID 70500776, compound

HRID 1415416Notes

Reaction equation

HRID 1415416 reaction equation
[CH2:1]1[CH2:5]OC[CH2:2]1.NN.S1C=CC=[C:9]1CC(Cl)=O.[CH3:17][C:18]([O:20][CH2:21][C:22]1[CH2:39][S:38][C@@H:25]2[C@H:26]([NH:29][C:30]([CH2:32][C:33]3[S:37][CH:36]=[CH:35][CH:34]=3)=[O:31])[C:27](=[O:28])[N:24]2[C:23]=1[C:40]([OH:42])=[O:41])=[O:19]>C(Cl)(Cl)Cl.CC#N>[S:37]1[CH:36]=[CH:35][CH:34]=[C:33]1[CH2:32][C:30]([NH:29][CH:26]1[C:27](=[O:28])[N:24]2[C:23]([C:40]([O:42][C:1]([CH3:2])([CH3:5])[CH3:9])=[O:41])=[C:22]([CH2:21][O:20][C:18](=[O:19])[CH3:17])[CH2:39][S:38][C@H:25]12)=[O:31]

Participants

7

Reactant 4

HCID 6024CephalothinHCID 8028TetrahydrofuranHCID 9321HydrazineHCID 1623622-Thiopheneacetyl chloride

Product 1

HCID 70500776HCID 70500776, compound

Reagents, catalysts & solvents 2

HCID 6212ChloroformSolventHCID 6342AcetonitrileSolvent

Procedure

A solution of 1.37 g. (3 mmol.) of t-butyl 7-phthalisoimido-3-acetoxymethyl-3-cephem-4-carboxylate in 10 ml. of dry THF was cooled in an ice water bath, and 0.12 ml. of anhydrous hydrazine was added. After the mixture was stirred for 5 min., 0.75 ml. of 2-thienylacetyl chloride was added, and the mixture was refluxed for 8 min., cooled and evaporated to dryness. The residue was dissolved in ethyl acetate, and the solution was washed successively with NaHCO3 solution, 1N HCl, water and brine. The crude mixture was chromatographed over silica gel using a gradient mixture of benzene and ethyl acetate. Fractions 16-73 were collected giving 340 mg. of t-butyl ester of cephalothin [α]D + 40.0° (MeCN); λEtOH 238 and 262 mμ (ε 14,200 and 8300); ir (CHCl3) 1785, 1740, 1730 and 1690 cm-1 ; nmr (CDCl3) δ 1.55 (s, 9, t-Bu), 2.1 (s, 3, CH3), 3.25 and 3.6 (ABq, 2, J = 17 Hz), 3.82 (s, 2, CH2), 4.75 and 5.14 (ABq, 2, CH2), 4.92 (d, 1, J = 4.5 Hz), 5.82 (dd, 1, J = 4.5 and 9 Hz), and 7.2 (m, 3, ArH).

Workup

  1. temperaturethe mixture was refluxed for 8 min.
  2. temperaturecooled
  3. customevaporated to dryness
  4. dissolutionThe residue was dissolved in ethyl acetate
  5. washthe solution was washed successively with NaHCO3 solution, 1N HCl, water and brine
  6. customThe crude mixture was chromatographed over silica gel using
  7. additiona gradient mixture of benzene and ethyl acetate
  8. customFractions 16-73 were collected
  9. customgiving 340 mg

Sources & evidence

ORD record
ord-80f4de390b9542729651e8797272fb31
Source dataset
uspto-grants-1977_01
Patent number
US04005074

Reaction notes

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