Citric Acid → tert-Butyl 4-((5-bromopyridin-2-yl)oxy)piperidine-1-carboxylate

HRID 1005866Notes

Reaction equation

[H-].[Na+].[C:3]([O:7][C:8]([N:10]1[CH2:15][CH2:14][CH:13]([OH:16])[CH2:12][CH2:11]1)=[O:9])([CH3:6])([CH3:5])[CH3:4].Br[C:18]1[CH:23]=[CH:22][C:21]([Br:24])=[CH:20][N:19]=1.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>CN1CCCC1=O>[C:3]([O:7][C:8]([N:10]1[CH2:15][CH2:14][CH:13]([O:16][C:18]2[CH:23]=[CH:22][C:21]([Br:24])=[CH:20][N:19]=2)[CH2:12][CH2:11]1)=[O:9])([CH3:6])([CH3:4])[CH3:5]

Participants

Conditions

Temperature: 70 °C

Procedure

Sodium hydride (0.20 g, 60% dispersion in mineral oil) was added to a solution of-4-hydroxypiperidine-1-car-boxylic-acid-tert-butyl ester (0.92 g) in anhydrous 1-methyl-2-pyrrolidinone (5 μl), precooled in ice. After stirring for 30 minutes under nitrogen, 2,5-dibromopyridine (1.0 g) was added. The reaction mixture was then stirred for two hours at room temperature before heating to 70° C. for four hours. The resultant dark mixture was poured onto ice (200 ml) containing 2% citric acid (20 ml), and was extracted with diethyl ether (3×15 ml). The aqueous phase was then basified to pH 13 with solid sodium hydroxide, and extracted with diethyl ether (2×15 ml). The combined organics were washed with water (3×20 ml), saturated brine (20 ml) and dried over anhydrous sodium sulfate and evaporated to give the title compound as a light brown oil (0.87 g, 58%).

Workup

stirringThe reaction mixture was then stirred for two hours at room temperature
additionThe resultant dark mixture was poured onto ice (200 ml)
extractionwas extracted with diethyl ether (3×15 ml)
extractionextracted with diethyl ether (2×15 ml)
washThe combined organics were washed with water (3×20 ml), saturated brine (20 ml)
dry with materialdried over anhydrous sodium sulfate
customevaporated

Sources & evidence

ORD record: ord-90549c689ae341229fd2d43c28544019
Source dataset: uspto-grants-2004_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06787536B2

Reaction notes

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