Methanol → 7-Aminocephalosporanic acid

HRID 1731702Notes

Reaction equation

HRID 1731702 reaction equation
P(Cl)(Cl)(Cl)(Cl)Cl.N1C=CC=C[CH:8]=1.C1(CC([NH:22][CH:23]2[C:47](=[O:48])[N:25]3[C:26]([C:34]([O:36]CC4C=CC([N+]([O-])=O)=CC=4)=[O:35])=[C:27]([CH2:30]SC=C)[CH2:28][S:29][C@H:24]23)=O)C=CC=CC=1.CO.[C:51](=[O:54])(O)[O-:52].[Na+]>C(Cl)Cl>[CH3:8][C:51]([O:52][CH2:30][C:27]1[CH2:28][S:29][C@@H:24]2[C@H:23]([NH2:22])[C:47](=[O:48])[N:25]2[C:26]=1[C:34]([OH:36])=[O:35])=[O:54]

Participants

6

Reactant 4

HCID 887MethanolHCID 516892Sodium BicarbonateHCID 10946106Phosphorane, pentachloro-, compd. with pyridine (1:1)HCID 67894746HCID 67894746, compound

Product 1

HCID 4413287-Aminocephalosporanic acid

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a suspension of phosphorus pentachloride-pyridine complex (prepared from phosphorus pentachloride (1.31 g) and pyridine (0.508 ml)) in methylene chloride was added p-nitrobenzyl 7-(2-phenylacetamido)-3-vinylthiomethyl-3-cephem-4-carboxylate (1.10 g) at -20° C. The mixture was stirred for 20 minutes under ice-cooling and poured into methanol (20 ml), and then an aqueous solution of sodium bicarbonate (2.1 g) was added thereto. The organic layer was separated at pH 4, washed with water, an aqueous solution of sodium bicarbonate and a saturated aqueous solution of sodium chloride successively and dried over magnesium sulfate. The inorganic material was filtered off, and to the filtrate was added bis(trimethylsilyl)urea (5.93 g). The mixture was stirred at 30° C. for 15 minutes to give a solution of the silylated 7-aminocephalosporanic acid derivative. On the other hand, phosphorus oxychloride (0.442 g) was added to a solution of N,N-dimethylformamide (0.207 ml) in ethyl acetate (0.65 ml) under ice-cooling. The mixture was stirred at the same temperature for 30 minutes. To the mixture were added 2-(p-nitrobenzyloxycarbonylmethoxyimino)-2-[2-(2,2,2-trifluoroacetamido)thiazol-4-yl]acetic acid (syn isomer) (1.14 g), methylene chloride (55 ml) and tetrahydrofuran (2 ml) at the same temperature and the mixture was stirred for 30 minutes to give an activated acid solution. This solution was added to the solution of the silylated 7-aminocephalosporanic acid derivative at -20° C. The mixture was stirred at -20°~-10° C. for 30 minutes, poured into ice-water and adjusted to pH 7 with an aqueous solution of sodium bicarbonate. The organic layer was separated, washed with a diluted aqueous solution of sodium bicarbonate, water and a saturated aqueous solution of sodium chloride in turn, dried over magnesium sulfate and concentrated in vacuo. The residue was purified by silica gel (25 g) column chromatography using a mixture of chloroform and methanol (50:1) as an eluent to give p-nitrobenzyl 7-[2-(p-nitrobenzyloxycarbonylmethoxyimino)-2-{2-(2,2,2-trifluoroacetamido)thiazol-4-yl}acetamido]-3-vinylthiomethyl-3-cephem-4-carboxylate (syn isomer) (1.23 g).

Workup

  1. temperaturecooling
  2. customThe organic layer was separated at pH 4
  3. washwashed with water
  4. dry with materialan aqueous solution of sodium bicarbonate and a saturated aqueous solution of sodium chloride successively and dried over magnesium sulfate
  5. filtrationThe inorganic material was filtered off
  6. additionto the filtrate was added bis(trimethylsilyl)urea (5.93 g)
  7. stirringThe mixture was stirred at 30° C. for 15 minutes

Sources & evidence

ORD record
ord-4cc58413ffa649dc9b602c2b1ddff83c
Source dataset
uspto-grants-1986_11
Patent number
US04622318

Reaction notes

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