Wednesday, November 2, 2011

Process Wednesday: removing boron as trimethylborate

From a Organic Process Research and Development ASAP, a quick aside about the removal of traces of boron [1] after a borane reduction:
After heating to complete the [borane] reduction, the reaction mixture was quenched into methanol and distilled to remove some of the boron as trimethylborate.
Trimethylborate has a boiling point of 68°C-69°C, according to Wikipedia. A perusal of the literature provides a nice explanation of how this works [2]:
In this salt-free process, all traces of boron are conveniently removed from the reaction mixture as trimethylborate by full displacement in methanol. The trimethylborate forms an azeotrope with methanol (70% B(OMe)3 at 59 °C), and under these conditions, even boric acid can be removed from the reaction mixture. (Schlesinger, H. I.; Brown, H. C.; Mayfield, D. L.; Gilbreath, J. R. J. Am. Chem. Soc. 1953, 75, 213.)
Maybe everyone else knew about this, but I didn't.

1. Sieser, J.E. et al. Org. Process. Res. Dev. 10.1021/op2001854
2. Couturier, M. et al. Org. Process. Res. Dev. 2002, 6, 42-48. 


  1. This also works well after a BBr3 deprotection. I used to demethylate eight methoxy groups at once, which is a lot of boron. Repeatedly rinsing with methanol and rotavapping helped clean it up nicely.

  2. Dear Sir,
    Could you please give details of work-up. I also did demethylation step by BBr3. After work-up I got spot at the base in TLC, this may be due to boric acid. I have tried by digesting solid obtained in IPA. But still boric acid is present and I lost some compound in IPA.
    I hope in your case, the material is insoluble in methanol.
    Please help