Methanol → (6R,7R)-Benzhydryl 7-amino-3-((1-methyl-1H-tetrazol-5-ylthio)methyl)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate

HRID 1707202Notes

Reaction equation

HRID 1707202 reaction equation
P(Cl)(Cl)(Cl)(Cl)Cl.N1C=CC=C[CH:8]=1.C[CH:14]([S:49][C:50]1[NH:54][N:53]=[N:52][N:51]=1)[C:15]1[CH2:16][S:17][C@@H:18]2[C@H:38]([NH:39]C(=O)CC3SC=CC=3)[C:37](=[O:48])[N:19]2[C:20]=1[C:21]([O:23][CH:24]([C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1)[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)=[O:22].CO>C(Cl)Cl>[NH2:39][C@@H:38]1[C:37](=[O:48])[N:19]2[C:20]([C:21]([O:23][CH:24]([C:31]3[CH:32]=[CH:33][CH:34]=[CH:35][CH:36]=3)[C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)=[O:22])=[C:15]([CH2:14][S:49][C:50]3[N:54]([CH3:8])[N:53]=[N:52][N:51]=3)[CH2:16][S:17][C@H:18]12

Participants

6

Reactant 4

HCID 887MethanolHCID 1049PyridineHCID 24819Phosphorus pentachlorideHCID 178477370HCID 178477370, compound

Product 1

HCID 12873516(6R,7R)-Benzhydryl 7-amino-3-((1-methyl-1H-tetrazol-5-ylthio)methyl)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylateYield 81.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Procedure

A suspension of phosphorus pentachloride (416 mg) in dry methylene dichloride (10 ml.) was stirred at 23° and a solution of pyridine (0.16 ml) added. The warm suspension was stirred for 10 minutes, and cooled to 0°, and treated, over 10 minutes, with a solution of diphenylmethyl 3-(1-methyltetrazol-5-ylthiomethyl)-7β-(2-thienylacetamido)-ceph-3-em-4-carboxylate (619 mg) in methylene dichloride (15 ml.). After stirring for a further 45 minutes, during which time the temperature was allowed to rise to 23°, the solution was added, over 5 minutes, to a stirred and cooled (0°) mixture of methanol (5 ml.) and methylene dichloride (15 ml.). The resulting solution was stirred for a further 10 minutes, and washed with N-hydrochloric acid (20 ml.), and stirred for 30 minutes with saturated sodium bicarbonate sodium (50 ml.). The organic phase was separated, and washed with saturated aqueous sodium bicarbonate (25 ml.), and treated with some charcoal. The mixture was filtered through a pad of kieselguhr, and the filtrate evaporated to a gum (640 mg.), which was triturated with ether (20 ml) to give the amine as an off-white solid (403 mg, 81.5%), λmax. (CHCl3) 268.5 nm (ε 7,700), νmax. (CHBr3) 3416 and 3350 (NH2), 1780 (β-lactam), and 1720 cm.-1 (CO2R), τ (CDCl3) values include 5.00 and 5.15 (C-6H and C-7 H, two doublets, J 5 Hz.), 6.14 (CH3 --), and 7.59 (NH2).

Workup

  1. stirringThe warm suspension was stirred for 10 minutes
  2. temperaturecooled to 0°
  3. stirringAfter stirring for a further 45 minutes, during which time the temperature
  4. customto rise to 23°
  5. additionthe solution was added, over 5 minutes
  6. stirringto a stirred
  7. temperaturecooled
  8. stirringThe resulting solution was stirred for a further 10 minutes
  9. washwashed with N-hydrochloric acid (20 ml.)
  10. stirringstirred for 30 minutes with saturated sodium bicarbonate sodium (50 ml.)
  11. customThe organic phase was separated
  12. washwashed with saturated aqueous sodium bicarbonate (25 ml.)
  13. additiontreated with some charcoal
  14. filtrationThe mixture was filtered through a pad of kieselguhr
  15. customthe filtrate evaporated to a gum (640 mg.), which
  16. customwas triturated with ether (20 ml)

Sources & evidence

ORD record
ord-3ea830dc85414b89a931f935e580dce1
Source dataset
uspto-grants-1980_06
Patent number
US04209616

Reaction notes

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