Phosphate → 7beta-(2-Hydroxyimino-2-phenylacetamido)-3-hydroxymethyl-ceph-3-em-4-carboxylic acid sodium salt

HRID 2398137Notes

Reaction equation

HRID 2398137 reaction equation
C([O:4][CH2:5][C:6]1[CH2:7][S:8][C@@H:9]2[C@H:16]([NH:17][C:18](=[O:28])[C:19](=[N:26][OH:27])[C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)[C:15](=[O:29])[N:10]2[C:11]=1[C:12]([OH:14])=[O:13])(=O)C.C(=O)(O)[O-].[Na+:34].[OH-].[Na+].P([O-])([O-])([O-])=O>CC(C)=O.O>[Na+:34].[OH:27][N:26]=[C:19]([C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)[C:18]([NH:17][C@@H:16]1[C:15](=[O:29])[N:10]2[C:11]([C:12]([O-:14])=[O:13])=[C:6]([CH2:5][OH:4])[CH2:7][S:8][C@H:9]12)=[O:28]

Participants

7

Reactant 4

HCID 1061PhosphateHCID 14798Sodium HydroxideHCID 516892Sodium BicarbonateHCID 88767746HCID 88767746, compound

Product 1

HCID 1317107547beta-(2-Hydroxyimino-2-phenylacetamido)-3-hydroxymethyl-ceph-3-em-4-carboxylic acid sodium salt

Reagents, catalysts & solvents 2

HCID 180AcetoneSolventHCID 962WaterSolvent

Procedure

To 3-acetoxymethyl-7β-(2-hydroxyimino-2-phenyl-acetamido)ceph-3-em-4-carboxylic acid (syn-isomer) (5.0 g) was added sufficient saturated sodium bicarbonate solution to bring the pH to 7.0, during which time solution occurred. To this solution was added water (300 ml) and defatted wheat germ (35 g.), and the suspension stirred vigorously whilst the pH was maintained at between 6.7 and 6.9 by frequent additions of 2N-sodium hydroxide. After addition of ca. 6 ml, the pH remained constant at 6.9. The mixture was poured into acetone (400 ml.), filtered (kieselguhr), and the filtrate evaporated under reduced pressure to remove acetone, then refiltered (kieselguhr). The filtrate was washed with ethyl acetate, and the pH adjusted to 2.8. The aqueous phase was extracted with ethyl acetate, and the extracts were stirred with water (ca. 300 ml) and the pH brought up to 7.0 with 2N sodium hydroxide. The phases were separated and the aqueous phase washed twice with ethyl acetate, once with ether, evaporated under reduced pressure to remove residual solvents, and freeze-dried. This gave the title acid (1.5 g; 31%), [α]D + 93° (c 1.0, DMSO), λmax. (pH 6 phosphate butter) 252 nm (ε 12,800), νmax. (Nujol) 1750 (β-lactam), 1650 and 1530 cm.-1 (amide), τ (DMSO-d6) values include 2.3 to 2.6 (multiplet; aromatic protons): 5.72 and 6.05 [two doublets (branches of a quartet), J 13 Hz CH2OH], 6.44 and 6.44 and 6.68 [two doublets (branches of a quartet), J 18 Hz; C-2 CH2 ].

Workup

  1. additionAfter addition of ca. 6 ml
  2. filtrationfiltered (kieselguhr)
  3. customthe filtrate evaporated under reduced pressure
  4. customto remove acetone
  5. washThe filtrate was washed with ethyl acetate
  6. extractionThe aqueous phase was extracted with ethyl acetate
  7. stirringthe extracts were stirred with water (ca. 300 ml)
  8. customThe phases were separated
  9. washthe aqueous phase washed twice with ethyl acetate, once with ether
  10. customevaporated under reduced pressure
  11. customto remove residual solvents
  12. customfreeze-dried
  13. customThis gave the title acid (1.5 g; 31%), [α]D + 93° (c 1.0, DMSO), λmax

Sources & evidence

ORD record
ord-0cb00c0fe6a6484c9f03f0dba47f3ced
Source dataset
uspto-grants-1977_05
Patent number
US04024134

Reaction notes

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