Benzophenone imine → 4-[6-(Benzhydrylidene-amino)-pyridin-2-yloxy]-2-methyl-piperidine-1-carboxylic acid tert-butyl ester

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Reaction Conditions

Reaction Steps

Combine 4-(6-chloro-pyridin-2-yloxy)-2-methyl-piperidine-1-carboxylic acid tert-butyl ester cis isomer 1 (preparation 49, 4.50 g, 13.77 mmol), toluene (150 mL), benzhydrylideneamine (3.0 g, 16.52 mmol), sodium-t-butoxide (1.85 g, 19.28 mmol), and 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (0.343 g, 0.55 mmol), stir and heat at 100° C. After 10 min., add tris(dibenzylideneacetone)-dipalladium(0) (0.252 g, 0.275 mmol), stir and heat at 100° C. After 3 hr., cool to ambient temperature. Partition between water (200 mL) and 4:1 hexane:ethyl acetate (200 mL). Separate the aqueous fraction and wash again with 4:1 hexane:ethyl acetate (200 mL). Dry the combined organic layers over sodium sulfate, filter and concentrate. Purify the residue by silica gel flash chromatography eluting with 9:1:0.2 hexane:ethyl acetate:2M ammonia/methanol to obtain the title compound (6.08 g, 94%). 1H NMR (CDCl3): 7.8 (d, 2H), 7.45 (m, 4H), 7.3 (m, 3H), 7.2 (m, 2H), 6.3 (dd, 2H), 5.1 (m, 1H), 4.2 (m, 1H), 3.8 (m, 1H), 3.2 (m, 1H), 1.6 (m, 4H), 1.5 (s, 9H), 1.2 (d, 3H).

Provenance & Evidence