(Bromomethyl)cyclobutane → 2,5-Dichloro-4-cyclobutylmethoxy-pyridine

HRID 1480052Notes

Reaction equation

HRID 1480052 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([OH:8])[C:5]([Cl:9])=[CH:4][N:3]=1.CC(C)([O-])C.[Na+].Br[CH2:17][CH:18]1[CH2:21][CH2:20][CH2:19]1>C1COCC1.CN(C=O)C>[Cl:1][C:2]1[CH:7]=[C:6]([O:8][CH2:17][CH:18]2[CH2:21][CH2:20][CH2:19]2)[C:5]([Cl:9])=[CH:4][N:3]=1

Participants

6

Reactant 3

HCID 2734658(Bromomethyl)cyclobutaneHCID 23676156Sodium t-butoxideHCID 178516192HCID 178516192, compound

Product 1

HCID 902038952,5-Dichloro-4-cyclobutylmethoxy-pyridineYield 50%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of 2,5-dichloro-4-pyridinol (CAN 847664-65-7, 660 mg, 4.02 mmol) in THF (20 mL) and DMF (20 mL) was added with stirring sodium tert-butoxide (1.16 g, 12.1 mmol) and (bromomethyl)-cyclobutane (CAN 17247-58-4, 2.26 mL, 20.1 mmol). The resulting mixture was stirred at 80° C. for 20 h, cooled and concentrated. The residue was partitioned between water and ethyl acetate; the organic portions were combined, dried over Na2SO4, filtered and concentrated. The crude material was purified by flash chromatography (silica, heptane/ethyl acetate gradient) to give the title compound (466 mg, 50%) as white solid. LC-MS (UV peak area, m/z) 97.8%, 232.0293 (MH+).

Workup

  1. temperaturecooled
  2. concentrationconcentrated
  3. customThe residue was partitioned between water and ethyl acetate
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude material was purified by flash chromatography (silica, heptane/ethyl acetate gradient)

Sources & evidence

ORD record
ord-531253a6cfea4d798a784e11e0f7aa4c
Source dataset
uspto-grants-2016_08
Patent number
US09409866B2

Reaction notes

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