Microbial hydroxylation of o-bromophenylacetic acid: synthesis of 4-substituted-2,3-dihydrobenzofurans

Abstract

Microbial hydroxylation of o-bromophenylacetic acid provided 2-bromo-5-hydroxyphenylacetic acid. This enabled a route to the key intermediate 4-bromo-2,3-dihydrobenzofuran for synthesizing a melatonin receptor agonist and sodium hydrogen exchange compounds. Pd-mediated coupling reactions of 4-bromo-2,3-dihydrobenzofuran provided easy access to the 4-substituted-2,3-dihydrobenzofurans.

2-(2-Chlorophenyl)acetic acid

“…Data collection: CrysAlis PRO (Oxford Diffraction, 2010); cell refinement: CrysAlis PRO; data reduction: CrysAlis PRO; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: ORTEP-3 for Windows (Farrugia, 1997); software used to prepare material for publication: PLATON (Spek, 2009 Derivatives of phenyl acetic acids are used as ingredients in perfume to provide honey like odour, for the preparation of a nonsteroidal anti-inflammatory drug like diclofenac (Hata et al, 1986;Castellari & Ottani, 1995), and as intermediate compounds for the synthesis of heterocyclic compounds (Deshpande et al, 2008). In continuation of our work on substituted phenylacetic acid (Kant et al, 2012), we report the crystal structure of a new derivative, 2-(2-chlorophenyl)-acetic acid (I).…”

“…For applications of phenylacetic acids, see: Castellari & Ottani (1995); Deshpande et al (2008); Hata et al (1986). For the crystal structure of isostructural 2-(2-bromophenyl)acetic acid, see: Kant et al (2012).…”

2-(2-Bromophenyl)acetic acid

“…For applications of the title compound, see: Deshpande et al (2008); Rodriguesa et al (2002); Pratt et al (2000). For related structures, see: Hodgson & Asplund (1991); Harris et al (1994); Hartung et al (2004); Yuan et al (2008); Jasinski et al(2010); Li et al (2010).…”

“…The title compound, (I), has many applications in various syntheses, for example, in the synthesis of heterocyclic compounds (Deshpande et al, 2008) and in the synthesis of AMPA antagonists -substituted quinoxalinediones, quinolones, isatinoximes and benzodiazepine derivatives (Pratt et al, 2000). It can also be used in a gas chromatography as a phase transfer catalyst (Rodriguesa et al, 2002).…”

Bioreductive production of enantiopure (S)-duloxetine intermediates catalyzed with ketoreductase ChKRED15

“…The bioreduction serves as a powerful approach for the production of optically active alcohols, which are widely used as fundamental intermediates for pharmaceuticals, agrochemicals and other products with chiral centers [1][2][3][4][5][6]. With the increased availability of recombinant ketoreductases, industrial-scale processes using cell-free enzymes coupled with efficient recycling systems have been developed rapidly in the past decade, which provides high volumetric productivity, excellent stereoselectivity, absence of side reactions and other economic advantages [7][8][9][10][11][12].…”