Amine synthesis

A mixture of {(R)-5-[(3-fluoro-5-trifluoromethyl-benzenesulfonyl)-methyl-amino]- 5,6,7,8-tetrahydro-naphthalen-1 -yloxy}-acetic acid tert-butyl ester (87 mg, 0.168 mmol), sodium hydride (60%wt) (34 mg, 0.84 mmol) and diethylamine (175 μl, 1.68 mmol) in N-N-dimethylformamide (2 ml) was heated at 150°C in a microwave oven for 45 minutes. To the reaction mixture was added water (10 ml), and the resulting solution was extracted with ethyl acetate (3 * 20 ml). The combined organic layers were dried over sodium sulfate, filtered, and then concentrated to afford {(R)-5-[(3-diethylamino-5-thfluoromethyl-benzenesulfonyl)- methyl-amino]-5,6,7,8-tetrahydro-naphthalen-1-yloxy}-acetic acid te/t-butyl ester, which was used in the next step without purification. 


Patent reference: WO2010018112 (Roche)

A 20 mL microwave vial was charged with ethyl 6-chloro-5-cyano-2-methylnicotinate (5 g, 22.3 mmol), tert-butyl piperidine-4-carboxylate (4.11 g, 22.3 mmol), TEA (4.5 g, 44.5 mmol) and MeCN and heated, single nodeheating, to 100°C for 5 minutes. The reaction was concentrated and MeCN/water was added to precipitate the product. Filtration of the solid and drying gave ethyl 6-[4-(tert-butoxycarbonyl)piperidin-l-yl]-5-cyano-2- methylnicotinate as an orange colored solid. Yield: 6.99 g (77%).


Patent reference: WO2010005385 (Astrazeneca)

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