Methanol → 111390-01-3

HRID 1607998Notes

Reaction equation

HRID 1607998 reaction equation
C[Si]([NH:5][CH:6]1[C:22](=[O:23])[N:8]2[C:9]([C:15]([O:17][Si](C)(C)C)=[O:16])=[C:10]([CH2:13][I:14])[CH2:11][S:12][C@H:7]12)(C)C.[CH3:24][N:25]1[CH2:29][CH2:28][CH2:27][CH2:26]1.CO>>[IH:14].[NH2:5][C@@H:6]1[C:22](=[O:23])[N:8]2[C:9]([C:15]([O-:17])=[O:16])=[C:10]([CH2:13][N+:25]3([CH3:24])[CH2:29][CH2:28][CH2:27][CH2:26]3)[CH2:11][S:12][C@H:7]12

Participants

4

Reactant 3

HCID 887MethanolHCID 84541-MethylpyrrolidineHCID 12985331HCID 12985331, compound

Product 1

HCID 13591237111390-01-3Yield 66%

Procedure

To the filtrate containing the trimethylsilyl 7-(trimethylsilyl)amino-3-iodomethylceph-3-em-4-carboxylate at 0°-5° C. under an inert atmosphere of dry nitrogen was added 3.82 ml (36.7 mmoles, 1.0 equivalent) of 97% N-methylpyrrolidine (dried over molecular sieves) dropwise by syringe at such a rate so as to maintain a reaction temperature of less than 10° C. The resulting slurry was stirred an additional 15 minutes at 0°-5° C. After this time. 5.0 ml (123 mmoles, 3.35 equivalent) of methanol was added dropwise while maintaining a reaction temperature of less than 10° C. The resulting thin slurry was stirred an additional 15 minutes at 0°-5° C. The solid was suction filtered, washed with Freon TF (1×100 ml) and partially dried under suction for 15 minutes. Further drying in vacuo at ambient temperature to constant weight afforded 10.27 g (66%) of (6R,7R)-7-amino-3-(1-methyl-1-pyrrolidinio)methylceph-3-em-4-carboxylate monohydroiodide. The 360 MHz 1H NMR spectrum of this crude material (D2O) showed a Δ3 /Δ2 isomer ratio of 5.4/1; the HPLC chromatogram of the salt showed a Δ3 /Δ2 area % ratio of 8.1/1. The activity yield for the conversion of 7-ACA to 7-amino-3-(1-methyl-1-pyrrolidinio)methylceph-3-em-4-carboxylate was 43.5% (determined by HPLC quantitation of the salt versus a reference standard of the desired Δ3 isomer).

Workup

  1. temperatureto maintain a reaction temperature of less than 10° C
  2. temperaturewhile maintaining a reaction temperature of less than 10° C
  3. stirringThe resulting thin slurry was stirred an additional 15 minutes at 0°-5° C
  4. filtrationfiltered
  5. washwashed with Freon TF (1×100 ml)
  6. custompartially dried under suction for 15 minutes
  7. customFurther drying in vacuo at ambient temperature to constant weight

Sources & evidence

ORD record
ord-71f253e437d54f959e61d8fa536afd6d
Source dataset
uspto-grants-1989_09
Patent number
US04868294

Reaction notes

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