Isopropanol → 5-Bromo-2-(1-methylethoxy)pyridine

HRID 404916Notes

Reaction equation

HRID 404916 reaction equation
[CH:1]([OH:4])([CH3:3])[CH3:2].[H-].[Na+].F[C:8]1[CH:13]=[CH:12][C:11]([Br:14])=[CH:10][N:9]=1>CN(C)C=O.CCOCC>[Br:14][C:11]1[CH:12]=[CH:13][C:8]([O:4][CH:1]([CH3:3])[CH3:2])=[N:9][CH:10]=1

Participants

6

Reactant 3

HCID 3776IsopropanolHCID 24758Sodium hydrideHCID 27831685-Bromo-2-fluoropyridine

Product 1

HCID 219350685-Bromo-2-(1-methylethoxy)pyridineYield 92%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
130 °C

Procedure

To isopropanol (11 mL, 143 mmol) under nitrogen at 25° C. was added sodium hydride (95%, 1.94 g, 76.7 mmol) portion wise over 5 minutes. The reaction was stirred for 16 hours and a solution of 2-fluoro-5-bromopyridine (9 g, 51 mmol) in N,N-dimethyl formamide (250 mL) was added over 10 minutes. The resulting mixture was heated at 130° C. for 4 hours and cooled to 25° C. The mixture was diluted with ether (500 mL) and washed with water (600 mL) and brine (300 mL). The organic layer was dried (MgSO4), filtered, and concentrated to provide 10.1 g of the title compound (92%) as light yellow liquid. 1H NMR (300 MHz, DMSO-d6) δ ppm 1.28 (d, J=6.25 Hz, 6H) 5.08-5.28 (m, 1H) 6.75 (d, J=8.82 Hz, 1H) 7.86 (dd, J=8.82, 2.57 Hz, 1H) 8.26 (d, J=2.57 Hz, 1H); MS (ESI) m/z 217.9 (M+H)+.

Workup

  1. temperaturecooled to 25° C
  2. washwashed with water (600 mL) and brine (300 mL)
  3. dry with materialThe organic layer was dried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-7f2bdf6fea4e41539f8c5a4b2ea3f98f
Source dataset
uspto-grants-2014_06
Patent number
US08748627B2

Reaction notes

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