Reaction #55420

Reaction equation

7β-amino-7α-methoxy-3-[1-(2-t-butoxycarbonylethyl)tetrazol-5-ylthiomethyl]-3-cephem-4-carboxylic acid t-butyl ester

N,N-diethylaniline

→

7β-D-Mandelamido-7α-methoxy-3-[1-(2-carboxyethyl)tetrazol-5-ylthiomethyl]-3-cephem-4-carboxylic acid

Solvents

methylene chloride

methylene chloride

Conditions

Workup

1. 1
   workup.STIRRINGstirred for an additional 30 minutes
2. 2
   WashThe solution is washed with 50 ml
3. 3
   Dryingof cold 5% aqueous sodium bicarbonate, dried
4. 4
   Otherevaporated to dryness
5. 5
   workup.DISSOLUTIONThe residue is dissolved in a mixture of 10 ml
6. 6
   workup.STIRRINGof m-dmethoxybenzene and stirred at ambient temperature for 2 hours
7. 7
   OtherThe excess trifluoroacetic acid is evaporated under vacuum
8. 8
   Otherthe residue is partitioned between 50 ml
9. 9
   OtherThe organic phase is separated
10. 10
    workup.STIRRINGThe aqueous phase is stirred at pH 9.3-9.5 for 30 minutes
11. 11
    Extractionextracted with 50 ml
12. 12
    ExtractionThe aqueous layer is extracted with three 50 ml
13. 13
    Dryingportions of ethyl acetate and the combined extracts are dried
14. 14
    Otherevaporated to a small volume
15. 15
    workup.ADDITIONPetroleum ether is added dropwise
16. 16
    Otherto precipitate the title compound which
17. 17
    Filtrationis collected by filtration
18. 18
    Otherdried

Procedure

A solution of 1.06 g. (2 mmol.) of 7β-amino-7α-methoxy-3-[1-(2-t-butoxycarbonylethyl)tetrazol-5-ylthiomethyl]-3-cephem-4-carboxylic acid t-butyl ester and 0.30 g. (2 mmol.) of N,N-diethylaniline in 100 ml. of dry methylene chloride is stirred at 0°-5° while 0.56 g. (2 mmol.) of D-O-dichloroacetylmandeloyl chloride in 10 ml. of methylene chloride is added dropwise over 10 minutes. The mixture is stirred in the cold for 30 minutes then warmed to room temperature and stirred for an additional 30 minutes. The solution is washed with 50 ml. of cold dilute hydrochloric acid and 50 ml. of cold 5% aqueous sodium bicarbonate, dried and evaporated to dryness. The residue is dissolved in a mixture of 10 ml. of trifluoroacetic acid and 2 ml. of m-dmethoxybenzene and stirred at ambient temperature for 2 hours. The excess trifluoroacetic acid is evaporated under vacuum and the residue is partitioned between 50 ml. of ether and 50 ml. of water and adjusted to pH 9.3-9.5 with 5% aqueous sodium carbonate. The organic phase is separated and discarded. The aqueous phase is stirred at pH 9.3-9.5 for 30 minutes, extracted with 50 ml. of ethyl acetate which is discarded, layered with fresh ethyl acetate and adjusted to pH 1.5 with dilute hydrochloric acid. The aqueous layer is extracted with three 50 ml. portions of ethyl acetate and the combined extracts are dried and evaporated to a small volume. Petroleum ether is added dropwise to precipitate the title compound which is collected by filtration and dried.

Source