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6th September 2011 @ 07:22
Scale up of (-)-Dibenzoyl-L-tartaric acid for the resolution of S-PZQamine
MNR6-1%20scheme.png

MNR6-1%20table.PNG

Hazard and Risk Assessment:
As for MNR5-1

Formation of anhydride intermediate (MNR6-1-INT)

MNR6-1-INT.png

A mixture L-(+)-tartaric acid (45.0 g, 300 mmol) and benzoyl chloride (122 mL, 1.05 mol) was heated to 130°C for 3 h and then allowed to cool to room temperature. The pale brown solid was washed with cold Et2O to give a white crystalline solid. The mother liquor was concentrated and the solid was washed with cold Et2O to give more white crystalline solid. Total solid recovered 103.72 g (303 mmol, >100%). *The crude anhydride was not dried under high vac and you could still smell traces of benzoyl chloride.

Hydrolysis of the anhydride

The anhydride (103.72 g) was dissolved in a mixture of toluene(300 mL) and water (30 mL) and heated to reflux for 2 h and allowed to cool to room temperature. The mixture was then concentrated under reduced pressure to give a thick, pale orange oil which was left to stand overnight. Some crystals formed but crude was still mainly oil. Crude taken up in a refluxing mixture of IPA/hexane (30%, 250 mL) and allowed to cool to room temperature then in an ice/water bath. Nothing crashed out and on cooling the a thick oil separated from the organic phase. This process was repeated but again no product crystallized out. The mixture was concentrated and stored in the freezer over the weekend. The pale yellow/clear oil was then taken up in warm CHCl3 (40°C) and then hexane was added and chilled in the freezer for 4 hours. What looked like product crashed out.

Filtered, washed with hexane and dried under high vac.

Yield: 76.35 g

The mother liquor was concentrated for to recrystallise a 2nd crop.
Taken up in warm CHCl3 and stored in the freezer overnight, filtered, washed with hexane and dried under high vac.

2nd Crop Yield: 29.03 g

Total product recovered: 105.38 g, 220 mmol, 73%

1H NMR MNR6-1

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Attached Files
MNR6-1 scheme.png
MNR6-1 table.PNG
MNR6-1-INT.png
mnr6-1.pdf
mnr06-1.zip