2-Bromo-3-methylpyridine → tert-butyl (3R)-3-[(3-methylpyridin-2-yl)amino]piperidine-1-carboxylate

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Test reaction using the conditions which were shown to work in EN07957-76 2016-02-26 14:30; Pd2(DBA)3 (14 mg) and BINAP (19 mg) was stirred in toluene (2.5 ml). 14:35; 2-bromo-3-methylpyridine (344 mg), sodium t-butoxide (334 mg), and the amine (526 mg) was added to the mixture. 14:40; Heating at 115 °C. 15:10; 81% product. 15:40; 81% product, No further progress was observed, probably because of lack of amine 15:50; Another 0.4 ml amine was added to the mixture. 16:15; No further progress by HPLC, reaction terminated. 50 microlitres of the mixture was evaporated and the residue was dissolved in methanol-d4 and 1H NMR was recorded. By 1H NMR the starting pyridine was consumed completely, as opposed to the HPLC-MS which indicated 16% starting material. 2016-02-29 10:35; Purification using 25-100% ethyl acetate in heptane over 6 column lengths on a 50 g column, detection at 300 nm and collection on threshold 50 mAU. Evaporation fo the fractions gave 480 mg oil. ee measurement showed 99.9% ee

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