Benzyl Bromide → p-Toluenesulfonic acid

6-Aminoenicillanic acid (64.9 g, 300 millimoles) was dispersed in dry methylene chloride (1,500 ml) at room temperature in an argon atmosphere, and triethylamine (60.7 g, 600 millimoles) was added to the dispersion with stirring, which was continued until a homogeneous solution was formed. Then, methyl acetoacetate (34.8 g, 300 millimoles) was dropped into the solution, and the mixture was stirred at room temperature for 3 hours and concentrated under a reduced pressure. The remaining oily product was dried under a reduced pressure, and dry N,N-dimethylformamide (700 ml) and benzyl bromide (54.7 g, 320 millimoles) were added thereto, the mixture then being stirred at room temperature for 3 hours. Distilled water (1,000 ml) was added to the mixture, which was subjected to extraction with methylene chloride-diethyl ether (1:5) mixture (4×300 ml), washed with water (2×300 ml) and brine (2×200 ml) and dried over magnesium sulfate. The solvent was removed under a reduced pressure, and the residue was dissolved in dry acetone (750 ml). p-Toluenesulfonic acid monohydrate (68.5 g, 360 millimoles) was added to the solution with stirring, and the mixture was stirred for 12 minutes. Diethyl ether (750 ml) was added to the mixture, and the crystal precipitated was recovered by filtration and washed with diethyl ether two times to obtain 83.7 g (58.2%) of a crude crystal. Recrystallization from a methanol/methylene chloride/diethyl ether mixed solvent gave 74.3 g (51.8%) of a p-toluenesulfonic acid salt of benzyl 6-aminopenicillanate.

1. additionwas added to the dispersion
2. customwas formed
3. stirringthe mixture was stirred at room temperature for 3 hours
4. concentrationconcentrated under a reduced pressure
5. additionwere added
6. stirringthe mixture then being stirred at room temperature for 3 hours
7. extractionwas subjected to extraction with methylene chloride-diethyl ether (1:5) mixture (4×300 ml)
8. washwashed with water (2×300 ml) and brine (2×200 ml)
9. dry with materialdried over magnesium sulfate
10. customThe solvent was removed under a reduced pressure
11. dissolutionthe residue was dissolved in dry acetone (750 ml)
12. stirringwith stirring
13. stirringthe mixture was stirred for 12 minutes
14. customthe crystal precipitated
15. filtrationwas recovered by filtration
16. washwashed with diethyl ether two times
17. customto obtain 83.7 g (58.2%) of a crude crystal
18. customRecrystallization from a methanol/methylene chloride/diethyl ether mixed solvent

ORD record

ord-be0460dc0a854d11994bed68fd42296c

Source dataset

uspto-grants-1989_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US04873301