3-Bromopyridine → 4-Hydroxy-4-(3-pyridyl)cyclohexanone ethylene acetal

HRID 475696Notes

Reaction equation

[Li]CCCC.Br[C:7]1[CH:8]=[N:9][CH:10]=[CH:11][CH:12]=1.[CH2:13]1[O:23][C:16]2([CH2:21][CH2:20][C:19](=[O:22])[CH2:18][CH2:17]2)[O:15][CH2:14]1>CCOCC.C1COCC1>[CH2:14]1[O:15][C:16]2([CH2:21][CH2:20][C:19]([OH:22])([C:7]3[CH:8]=[N:9][CH:10]=[CH:11][CH:12]=3)[CH2:18][CH2:17]2)[O:23][CH2:13]1

Participants

Conditions

Temperature: -20 °C

Procedure

To a solution of n-BuLi (2.5 M in hexanes, 88.4 mL, 221.0 mmol) in Et2O (250 mL) at −78° C. was added a chilled solution (−78° C.) of 3-bromopyridine (35 g, 221.0 mmol) in Et2O (125 mL) via cannula. After being stirred for 10 min, a solution of 1,4-cyclohexanedione monoethylene ketal (34.5 g, 221.0 mmol) in THF (125 mL) was added via cannula The reaction mixture was stirred for 1 h at −78° C., then slowly warmed to −20° C. over 1 h. The reaction was quenched by pouring into saturated aqueous NH4Cl, and the layers were separated. The aqueous layer was extracted with CH2Cl2 (100 mL×3) and the combined organic layers were washed with brine (200 mL), dried with MgSO4 and concentrated in vacuo. The crude product was triturated with Et2O to afford 4-hydroxy-4-(3-pyridyl)cyclohexanone ethylene ketal as a white solid.

Workup

stirringwas stirred for 1 h at −78° C.
customThe reaction was quenched
additionby pouring into saturated aqueous NH4Cl
customthe layers were separated
extractionThe aqueous layer was extracted with CH2Cl2 (100 mL×3)
washthe combined organic layers were washed with brine (200 mL)
dry with materialdried with MgSO4
concentrationconcentrated in vacuo
customThe crude product was triturated with Et2O

Sources & evidence

ORD record: ord-74d7cef076dc4f6f896cbef6fe08695f
Source dataset: uspto-grants-2014_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08637576B2

Reaction notes

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