Cyclobutanone → 1-(5-Bromopyridin-2-yl)cyclobutan-1-ol
Reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([Br:8])=[CH:4][N:3]=1.[Li]CCCC.[C:14]1(=[O:18])[CH2:17][CH2:16][CH2:15]1>C1(C)C=CC=CC=1>[Br:8][C:5]1[CH:6]=[CH:7][C:2]([C:14]2([OH:18])[CH2:17][CH2:16][CH2:15]2)=[N:3][CH:4]=1Participants
5
Reactant 3
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 0 °C
Procedure
To a solution of 2,5-dibromopyridine (4.74 g, 20.0 mmol) in toluene (200 mL) was added n-BuLi (1.2 eq) dropwise at −50° C. The mixture was stirred at that temperature for 40 min, then cooled to −78° C. before cyclobutanone (1.82 g, 26.0 mmol) was added dropwise. The reaction mixture was stirred at −78° C. for 1 h, then warmed to 0° C. and quenched with 40 mL of NH4Cl (sat.). The organic layer was separated and concentrated. The crude product was purified by a SiO2 column (0-40% EtOAc/Hexanes, Rf=0.7 in 50% EtOAc) to afford the titled compound as a red oil (3.11 g).
Workup
- additionwas added dropwise
- stirringThe reaction mixture was stirred at −78° C. for 1 h
- customquenched with 40 mL of NH4Cl (sat.)
- customThe organic layer was separated
- concentrationconcentrated
- customThe crude product was purified by a SiO2 column (0-40% EtOAc/Hexanes, Rf=0.7 in 50% EtOAc)
Sources & evidence
- ORD record
- ord-d2945a61b63b4b36960d45b7b0047851
- Source dataset
- uspto-grants-2016_01
- Patent number
- US09227971B2
Reaction notes
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