Methyl iodide → 2-Bromo-3-(1-methoxycyclobutyl)pyridine

HRID 1592403Notes

Reaction equation

HRID 1592403 reaction equation
[Br:1][C:2]1[C:7]([C:8]2([OH:12])[CH2:11][CH2:10][CH2:9]2)=[CH:6][CH:5]=[CH:4][N:3]=1.[H-].[Na+].[CH3:15]I>CN(C=O)C>[Br:1][C:2]1[C:7]([C:8]2([O:12][CH3:15])[CH2:11][CH2:10][CH2:9]2)=[CH:6][CH:5]=[CH:4][N:3]=1

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 772302671-(2-Bromopyridin-3-yl)cyclobutanol

Product 1

HCID 873328672-Bromo-3-(1-methoxycyclobutyl)pyridineYield 71%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of the above alcohol (410 mg, 1.80 mmol) in DMF (5 mL) was added NaH (60%, 108 mg, 2.70 mmol). After 1 h, MeI (0.23 mL, 3.60 mmol) was added. After 1.5 h, the reaction mixture was filtered and the filtrate was concentrated to afford an orange oil. Purification by flash column chromatography using hexanes/EtOAc (2:1) afforded 2-bromo-3-(1-methoxy-cyclobutyl)-pyridine as a pale yellow solid (308 mg, 71%). 1H NMR (CDCl3) δ 1.61-1.71 (m, 1H), 2.04-2.14 (m, 1H), 2.56 (t, 4H, J=7.5 Hz), 2.96 (s, 3H), 7.25-7.30 (m, 1H), 7.64 (dd, 1H, J=7.5, 2.1 Hz), 8.31 (dd, 1H, J=4.7, 1.8 Hz).

Workup

  1. waitAfter 1.5 h
  2. filtrationthe reaction mixture was filtered
  3. concentrationthe filtrate was concentrated
  4. customto afford an orange oil
  5. customPurification by flash column chromatography

Sources & evidence

ORD record
ord-5220e9cfb4dd40638ce1169874126be2
Source dataset
uspto-grants-2007_11
Patent number
US07291631B2

Reaction notes

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