2-Bromo-4-(trifluoromethyl)pyridine → Tert-butyl 4-((diphenylmethyleneamino)methyl)-4-(4-(trifluoromethyl)pyridin-2-ylcarbamoyl)piperidine-1-carboxylate
Reaction equation
CC(C)(C)OC(=O)N1CCC(CN=C(c2ccccc2)c2ccccc2)(C(N)=O)CC1.FC(F)(F)c1ccnc(Br)c1>C1COCCO1.CC(=O)O.CC(=O)O.CC1(C)c2cccc(P(c3ccccc3)c3ccccc3)c2Oc2c(P(c3ccccc3)c3ccccc3)cccc21.O=C([O-])[O-].[Cs+].[Cs+].[Pd]>CC(C)(C)OC(=O)N1CCC(CN=C(c2ccccc2)c2ccccc2)(C(=O)Nc2cc(C(F)(F)F)ccn2)CC1Participants
Reactant 2
Product 1
Reagents, catalysts & solvents 4
Conditions
- Temperature
- 90 °C
Procedure
tert-butyl 4-carbamoyl-4-((diphenylmethyleneamino)methyl)piperidine-1-carboxylate (500 mg, 1.19 mmol), 2-bromo-4-(trifluoromethyl)pyridine (268 mg, 1.19 mmol), and cesium carbonate (541 mg, 1.66 mmol) were suspended in dioxane (2 mL) . The reaction was purged with nitrogen for 10 minutes then 9,9-Dimethyl-4,5-bis(diphenylphosphino)xanthene (30.9 mg, 0.05 mmol) and palladium(II) acetate (7.99 mg, 0.04 mmol) were added. The reaction was heated at 90 °C for 48 hours. The reaction was cooled to room temperature, diluted with DCM, filtered and concentrated. The crude product was purified by flash silica chromatography, elution gradient 0 to 40% EtOAc in isohexane. Pure fractions were evaporated to dryness to afford tert-butyl 4-((diphenylmethyleneamino)methyl)-4-(4-(trifluoromethyl)pyridin-2-ylcarbamoyl)piperidine-1-carboxylate (480 mg, 71.4 %) as a white solid.
Sources & evidence
- ORD record
- ord-1d2fdaa081974f57a1f1449ebd3c7c9a
- Source dataset
- 750 AstraZeneca ELN dataset
- Original link
- View source
Reaction notes
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