Acetone → Ceftobiprole Medocaril Sodium

HRID 1977094Notes

Reaction equation

HRID 1977094 reaction equation
[N+](C1C=CC(O[C:11](=[O:21])[O:12][CH2:13][C:14]2[O:15][C:16](=[O:20])[O:17][C:18]=2[CH3:19])=CC=1)([O-])=O.[NH2:22][C:23]1[S:27][N:26]=[C:25](/[C:28](=[N:56]/[OH:57])/[C:29]([NH:31][C@@H:32]2[C:39](=[O:40])[N:38]3[C@@H:33]2[S:34][CH2:35][C:36](/[CH:44]=[C:45]2/[C:46](=[O:55])[N:47]([C@@H:50]4[CH2:54][CH2:53][NH:52][CH2:51]4)[CH2:48][CH2:49]/2)=[C:37]3[C:41]([OH:43])=[O:42])=[O:30])[N:24]=1.CC(C)=O>CS(C)=O>[NH2:22][C:23]1[S:27][N:26]=[C:25](/[C:28](=[N:56]/[OH:57])/[C:29]([NH:31][C@@H:32]2[C:39](=[O:40])[N:38]3[C@@H:33]2[S:34][CH2:35][C:36](/[CH:44]=[C:45]2/[C:46](=[O:55])[N:47]([C@@H:50]4[CH2:54][CH2:53][N:52]([C:11]([O:12][CH2:13][C:14]5[O:15][C:16](=[O:20])[O:17][C:18]=5[CH3:19])=[O:21])[CH2:51]4)[CH2:48][CH2:49]/2)=[C:37]3[C:41]([OH:43])=[O:42])=[O:30])[N:24]=1

Participants

5

Reactant 3

HCID 180AcetoneHCID 10756264(5-Methyl-2-oxo-1,3-dioxol-4-yl)methyl 4-nitrophenyl carbonateHCID 135413542Ceftobiprole

Product 1

HCID 135413544Ceftobiprole Medocaril SodiumYield 92.6%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

To a solution of 13.2 g (44.72 mmol) of carbonic acid 5-methyl-2-oxo-[1,3]dioxol4-ylmethyl ester 4-nitro-phenyl ester in 200 ml of dimethylsulfoxide are added 20.0 g of (6R,7R)-7-[(Z)-2-(5-amino-[1,2,4]thiadiazol-3-yl)-2-hydroxyimino-acetylamino]-8-oxo-3-[(E)-(R)-2-oxo-[1,3′]bipyrrolidinyl-3-ylidenemethyl]-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid. The mixture is stirred under argon at room temperature for 4 hours and 1000 ml of acetone are added. The slightly turbid solution is clarified by filtration over a fluted filter. To the clear motherliquour are added 34.0 ml (34 mmol) of a 1N solution of sodium-2-ethylcaproate in acetone at room temperature during 20 minutes. The slightly yellow suspension is stirred for 10 minutes at room temperature, the solid is collected by filtration, washed with 1000 ml of acetone and 1000 ml of n-pentane and dried under high vacuum. The product is suspended in 600 ml of acetone and stirred at room temperature for 2 hours. The product is collected by filtration and dried under high vacuum to yield 23.94 g of the title compound as an off-white powder.

Workup

  1. filtrationThe slightly turbid solution is clarified by filtration over a fluted filter
  2. additionTo the clear motherliquour are added 34.0 ml (34 mmol) of a 1N solution of sodium-2-ethylcaproate in acetone at room temperature during 20 minutes
  3. stirringThe slightly yellow suspension is stirred for 10 minutes at room temperature
  4. filtrationthe solid is collected by filtration
  5. washwashed with 1000 ml of acetone and 1000 ml of n-pentane
  6. customdried under high vacuum
  7. stirringstirred at room temperature for 2 hours
  8. filtrationThe product is collected by filtration
  9. customdried under high vacuum

Sources & evidence

ORD record
ord-c89cdd995c7247b4bce0cdd27e2d04ef
Source dataset
uspto-grants-2001_05
Patent number
US06232306B1

Reaction notes

Loading…