반응 #603
ord-4a5932c3579844d8b45d89bc150e08f1
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실험 절차
Repeat from Patent write up and cf _EN06741-39\Reaction_ **_Aim:-_ **to Prepare target for further use **. NB. the SM is either the (R,R) or (S,S) isomer** ethyl 2-(5-bromo-3-methoxypicolinoyl)cyclopropanecarboxylate (0.329 g, 1.00 mmol), 4-chloro-N-(cyclopropylmethyl)naphthalen-1-amine, HCl (0.323 g, 1.20 mmol), PALLADIUM(II) ACETATE (0.011 g, 0.05 mmol), rac-2,2'-bis(diphenylphosphino)-1,1'-binaphthalene (0.044 g, 0.07 mmol) and cesium carbonate (0.784 g, 2.41 mmol) were mixed in toluene (16 mL), purged with nitrogen and stirred in a sealed tube at 70 °C for 19 hours. The reaction mixture was diluted with EtOAc (20 ml), filtered through a celite pad and concentrated to give 902 mg brown oil. TLC (1 : 1 - EtOAc : n-heptane) see diagram UV only The residue was absorbed onto a samplet and purified on a 25 g Biotage SNAP column, eluting with a step-wise gradient from 0 : 10 to 4 : 6 EtOAc : n-heptane using a Thomson pump collecting 25 ml fractions. Pure fractions were evaporated to give 318 mg of orange solid - the product eluted with the 4 : 6 mixture. The front spot was probably binap bis oxide LCMS (pH = 3) Rt = 1.66 min (85% by UV), m/z: 479 (MH+). 1H NMR (DMSO-d6) - looks ok - Aromatics are ok - aliphatics more or less ok but 1 proton missing but there are a number of small peaks as well! **_Conclusion:_ \- **OK to use for further reactions - See EN06995-01