bromofluoromethane
Bromofluoromethane

Valliscor Capabilities for Bromofluoromethane

Bromofluoromethane (BFM) is a powerful reagent for the incorporation of fluoromethyl moieties. Using proprietary technology, Valliscor manufactures kilogram to commercial scale of high purity BFM (>99.9% pure) for the pharmaceutical industry in its Corvallis, Oregon production facility.  To find out more information on our offerings, please contact us at info@valliscor.com.

Alternate Names: BFM, bromofluoromethylene, CFC 31B1, R 31B1
Catalog #: VCBFM
CAS #: 373-52-4
Molecular Weight: 112.916
Density: 1.76 g/mL
Boiling Point: 19°C
1H NMR Spectra (CDCl3): 6.1 (d, J(F-H) = 48 Hz, 2H) ppm
13C NMR Spectra (CDCl3): 77.4 (d, J(C-F) = 247 Hz) ppm
19F NMR Spectra (CDCl3): -163.5 (t, J = 48.9 Hz) ppm
IR Spectra: Mol. Phys. 2006, 104, 3187-3192
Microwave Spectra: J. Mol. Spec. 2007, 241, 112-115
Wikipedia Link: http://en.wikipedia.org/wiki/Bromofluoromethane
Material Safety Data Sheet (MSDS) / Safety Data Sheet (SDS): [DOWNLOAD]
Downloadable Flyer on Valliscor’s Bromofluoromethane (BFM) Capabilities: [DOWNLOAD]


Fluticasone and Related Examples

The fluoromethyl moiety has proven useful in a range of pharmaceutically relevant targets and agrochemically-significant compounds. One of the first examples of the use of bromofluoromethane in the synthesis of a commercial product is in the fluoromethylation of a thioacid to manufacture fluticasone propionate by Glaxo (J. Med. Chem. 199437, 3717-3729) (Eq. 1).

use of bromofluoromethane to make fluticasone proprionate

 

 

 

Subsequently, bromofluoromethane has been shown to be generally useful in accessing other fluticasone-related molecules – including fluticasone furoate (PCT Int. Appl., WO2007114363 A2, 21 Dec, 2007) by GlaxoSmithKline (Eq. 2).

bromofluoromethane to make fluticasone furoate

 

Other companies have demonstrated the utility of bromofluoromethane to construct related scaffolds including Chiesi Farmaceutici’s pyrrolidine-containing glucocortosteroids (PCT Int. Appl., WO2011095535 A2, 11 Aug, 2011) (Eq. 3) and biaryl ether-containing glucocorticoids from Pfizer (PCT Int. Appl., WO2010136940 A1, 2 Dec, 2010) (Eq. 4).

bromofluoromethane

PET Imaging Examples

Bromofluoromethane (BFM) has also proven useful for accessing PET imaging molecules. BFM can be cross coupled with boronic esters to access fluoromethyl aromatic compounds (Bull. Chem. Soc. Jpn. 2012, 85, 1233-1238) (Eq. 5). Additionally, alkylation using phenolic nucleophiles such as the protected tyrosine derivative shown below provides a PET imaging precursor in good yield (PCT Int. Appl., WO2013001088, 3 Jan 2013) (Eq. 6).

bromofluoromethane.Equation5-6

 

Alkylation of Phenolic Compounds

Flouromethylation of phenols with bromofluoromethane has proven useful to provide access to a variety of compounds. Acadia Pharmaceuticals reported the synthesis of cannabinoid CB2 receptor active compounds using precursors containing fluoromethyl ethers (PCI Int. Appl., WO2008141249, 20 Nov 2008) (Eq. 7). Astrazeneca snyhesized oxabispidine compounds for treatment of cardiac arrhythmias derived from flouromethyl-alkylated aldehyde derivatives (PCT Int. Appl., WO2007069986 A1, 21 Jun, 2007) (Eq. 8).

bromofluoromethane.Equation7-8

Oxime Alkylation

Bromofluoromethane can be used to alkyl other oxygen nucleophiles including oximes as shown below (Eur. J. Med. Chem. 2012, 47, 619-625) (Eq. 9).

bromofluoromethane.Equation9

Enolate Alkylation

Bromofluoromethane has also been employed for fluoromethylation of enolates. Takeda Pharmaceutical Company reported the alkylation of cyanoazetidine using LDA in good yield (PCT Int. Appl., WO2010144486 A1, 16 Dec, 2010) to access JAK inhibitors (Eq. 10).

bromofluoromethane.Equation10

Incorporation into Heterocylces

Bromofluoromethane (BFM) can also be utilized to alkylate complex heterocycles. Francotte and co-workers used BFM to construct new potentiators of AMPA receptors (J. Med. Chem. 2013, 56, 7838-7850) (Eq. 11). Sinochem utilized bromofluoromethane to access the pyrazole derivative as potential broad spectrum insecticide (PCT Int. Appl., WO2012034403 A1, 22 Mar, 2012) (Eq. 12).

bromofluoromethane.Equation11-12