2,5-Dibromopyridine → tert-Butyl 4-[(5-bromopyridin-2-yl)amino]piperidine-1-carboxylate

HRID 2266693Notes

Reaction equation

Br[C:2]1[CH:7]=[CH:6][C:5]([Br:8])=[CH:4][N:3]=1.[C:9]([O:13][C:14]([N:16]1[CH2:21][CH2:20][CH:19]([NH2:22])[CH2:18][CH2:17]1)=[O:15])([CH3:12])([CH3:11])[CH3:10].C(N(C(C)C)CC)(C)C>CN1CCCC1=O>[C:9]([O:13][C:14]([N:16]1[CH2:21][CH2:20][CH:19]([NH:22][C:2]2[CH:7]=[CH:6][C:5]([Br:8])=[CH:4][N:3]=2)[CH2:18][CH2:17]1)=[O:15])([CH3:12])([CH3:10])[CH3:11]

Participants

Conditions

Temperature: 80 °C

Procedure

A tube was charged with 2,5-dibromopyridine (0.24 g, 1.0 mmol), 4-Amino-piperidine-1-carboxylic acid tert-butyl ester (0.22 g, 1.1 mmol), di-isopropylethylamine (0.19 mL, 1.1 mmol) and N-methylpyrrolidinone (1.0 mL). The tube was sealed and the mixture was heated at 80° C. overnight. The temperature was increased to 120° C. and heated overnight. The reaction was partitioned between ethyl acetate and water. The phases were separated and the aqueous phase was extracted with ethyl acetate. The combined organic phases were dried over MgSO4 and concentrated by rotary evaporation. The residue was purified by silica gel chromatography using gradient elution of ethyl acetate and hexanes to afford 4-(5-bromo-pyridin-2-ylamino)-piperidine-1-carboxylic acid tert-butyl ester (36 mg, 10%).

Workup

customThe tube was sealed
temperatureThe temperature was increased to 120° C.
temperatureheated overnight
customThe reaction was partitioned between ethyl acetate and water
customThe phases were separated
extractionthe aqueous phase was extracted with ethyl acetate
dry with materialThe combined organic phases were dried over MgSO4
concentrationconcentrated by rotary evaporation
customThe residue was purified by silica gel chromatography
washelution of ethyl acetate and hexanes

Sources & evidence

ORD record: ord-76e268e5476b4591967c5b350b50d392
Source dataset: uspto-grants-2010_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07858643B2

Reaction notes

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