Chloromandelates

Ema, T., Okita, N., Ide, S. and Sakai, T. (2007) Highly enantioselective and efficient synthesis of methyl (R)-o-chloromandelate with recombinant E. coli toward practical and green access to clopidogrel. Organic and Biomolecular Chemistry, 5 (8), 1175-1176. 

Table 8.9 Conversion of 2-chloromandelonitrile to 2-chloromandelic acid using Arthrobacter sp. F-73 nitrilase in water-co-solvent mixtures...

Chloroethyl benzoate, 30,11 a-Chloroethyl ethyl ether, 36, 60 Chlorohydroquinone, 35, 27 -Chloromandelic acid, 35,14 Chloromethylation, 30, 68 2-Chloro-2-methylcyclohexanone, 37, 8... 

Recombinant cells expressing a cloned ADH have also been used in a coupled enzyme method to efficiently produce the (R)-2-chloromandelate intermediate in the synthetic route to clopidogrel in 90 % yield and >99 % ee at 200 gL substrate concentration (Scheme 1.53). This procedure does not use hydrogen cyanide and, therefore, represents... 

Enantiose active and Efficient Synthesis of Methyl (R)-o-Chloromandelate 291... 

Solid NaCl (5.5 g) was added and the product was extracted with EtOAc (25 mL X 3). Phase separation was effected by centrifugation (3200 rpm, 10 min). The combined organic layers were dried over MgS04, filtered and concentrated under reduced pressure. Purification by silica-gel column chromatography (hexane/ EtOAc (10 1)) gave methyl (7 )-o-chloromandelate ((/ )- ) as a colorless oil (1.78 g, 89 %). 

Hydrolase Resolution of (R,S)-ethyl mandelate and (R,S)-ethyl 2-chloromandelate in phosphate buffer / iso-octane [68, 69]... 

Under similar conditions, />-chloromandelic acid melting at 119-120° was obtained from />-chloroacetophenone in 54% yield and />-iodomandelic acid melting at 135-136° from /j-iodo-acetophenone in 21% yield. 

Fig. 15 Whole cell biocatalytic synthesis of methyl (f )-o-chloromandelate...

Ema T, Ide S et al (2008) Highly efficient chemoenzymatic synthesis of methyl (R)-o-chloromandelate, a key intermediate for clopidogrel, via asymmetric reduction with recombinant Escherichia coli. Adv Synth Catal 350 2039-2044... 

Methyl (R)-o-chloromandelate represents the key building block for the synthesis of clopidogrel, a platelet aggregation inhibitor widely administered to atherosclerotic patients with the risk of a heart attack or stroke that are caused by the formation of a clot in the blood. The worldwide sales of this pharmaceutical... 

Fig. 45 Synthesis of methyl (/J)-o-chloromandelate as the main precursor of the pharmaceutical compound clopidogrel...

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