Pyridine → HCID 131709934, compound

HRID 1580500Notes

Reaction equation

HRID 1580500 reaction equation
[CH3:1][O:2][C:3]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[C:6]([CH2:13][C:14]2[CH:19]([C:20]([OH:22])=[O:21])[N:18]3[C:23](=[O:35])[C@@H:24]([NH:25][C:26](=[O:34])[CH2:27][C:28]4[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=4)[C@H:17]3[S:16][CH:15]=2)=[CH:5][CH:4]=1.N1C=CC=CC=1.[Cl:42][C:43]([Cl:47])([Cl:46])[CH2:44]O.C1(N=C=NC2CCCCC2)CCCCC1>C(Cl)Cl>[Cl:42][C:43]([Cl:47])([Cl:46])[CH2:44][O:21][C:20]([CH:19]1[N:18]2[C:23](=[O:35])[C@@H:24]([NH:25][C:26](=[O:34])[CH2:27][C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=3)[C@H:17]2[S:16][CH:15]=[C:14]1[CH2:13][C:6]1[C:7]2[C:12](=[CH:11][CH:10]=[CH:9][CH:8]=2)[C:3]([O:2][CH3:1])=[CH:4][CH:5]=1)=[O:22]

Participants

6

Reactant 4

HCID 1049PyridineHCID 8259TrichloroethanolHCID 10868DicyclohexylcarbodiimideHCID 131709935HCID 131709935, compound

Product 1

HCID 131709934HCID 131709934, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Procedure

A solution of 10.9 g of 3-(4-methoxy-1-naphthylmethyl)-7β-phenylacetylamino-ceph-2-em-4ξ-carboxylic acid in 300 ml of methylene chloride is treated with 1.80 ml of pyridine, then successively with 2.50 ml of 2,2,2-trichloroethanol in 20 ml of methylene chloride and 4.95 g of dicyclohexylcarbodiimide in 40 ml of methylene chloride. The addition of the reagents is carried out at room temperature and while stirring. The reaction mixture is stirred for 20 hours at room temperature, freed from dicyclohexylurea by means of filtration and the filtrate is evaporated under reduced pressure. The residue is taken up in ethyl acetate and mixed with an aqueous dipotassium hydrogen phosphate buffer solution (pH 7.5). The aqueous portion is separated, washed several times with ethyl acetate and the pH adjusted to 2.5 with 20% aqueous phosphoric acid. After repeated extraction with ethyl acetate, the organic extracts from the aqueous phase having pH 2.5 are combined, washed with water and a saturated aqueous sodium chloride solution, dried over magnesium sulphate and evaporated under reduced pressure. The residue is chromatographed on 450 g of silica gel, elution being carried out with methylene chloride containing 5% of methyl acetate, fractions of 500 ml being taken. The residue of the fractions 12-13 is crystallised from ethyl acetate and yields the 3-(4-methoxy-1-naphthylmethyl)-7β-phenylacetylamino-ceph-2-em-4ξ-carboxylic acid 2,2,2-trichloroethylester, which melts at 145-147°; [α]D20 = + 271° ± 1° (c = 0,918 in chloroform); ultraviolet absorption spectrum (in methanol): λmax = 210 mμ (ε = 67000), 232 mμ (ε = 41200), 298 mμ (ε = 9990) and 322 mμ (ε = 4960); infrared absorption spectrum (in mineral oil): characteristic bands at 2,90μ, 5,62μ, 5,68μ, 6,02μ, 6,27μ and 6,60μ; thin-layer chromatogram (silica gel): Rf = 0.27 (system: toluene/ethyl acetate 4:1) and Rf = 0.38 (system: toluene/acetone 9:1).

Workup

  1. additionThe addition of the reagents
  2. customis carried out at room temperature
  3. stirringThe reaction mixture is stirred for 20 hours at room temperature
  4. filtrationfreed from dicyclohexylurea by means of filtration
  5. customthe filtrate is evaporated under reduced pressure
  6. additionmixed with an aqueous dipotassium hydrogen phosphate buffer solution (pH 7.5)
  7. customThe aqueous portion is separated
  8. washwashed several times with ethyl acetate
  9. extractionextraction with ethyl acetate
  10. washwashed with water
  11. dry with materiala saturated aqueous sodium chloride solution, dried over magnesium sulphate
  12. customevaporated under reduced pressure
  13. customThe residue is chromatographed on 450 g of silica gel, elution
  14. customThe residue of the fractions 12-13 is crystallised from ethyl acetate

Sources & evidence

ORD record
ord-b9e12aaad0484b159ae1d4abd9769a26
Source dataset
uspto-grants-1976_01
Patent number
US03932465

Reaction notes

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