3-Bromopyridine → 2-Fluoro-4-(1-hydroxy-1-pyridin-3-yl-methyl)-benzonitrile

HRID 1060886Notes

Reaction equation

HRID 1060886 reaction equation
Br[C:2]1[CH:3]=[N:4][CH:5]=[CH:6][CH:7]=1.[Li]CCCC.[Li].[F:14][C:15]1[CH:22]=[C:21]([CH:23]=[O:24])[CH:20]=[CH:19][C:16]=1[C:17]#[N:18]>CCOCC.C1COCC1>[F:14][C:15]1[CH:22]=[C:21]([CH:23]([OH:24])[C:2]2[CH:3]=[N:4][CH:5]=[CH:6][CH:7]=2)[CH:20]=[CH:19][C:16]=1[C:17]#[N:18]

Participants

7

Reactant 4

HCID 122863-BromopyridineHCID 3028194LithiumHCID 112173392-Fluoro-4-formylbenzonitrileHCID 178418339Butyllithium

Product 1

HCID 186294522-Fluoro-4-(1-hydroxy-1-pyridin-3-yl-methyl)-benzonitrile

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

3-Bromopyridine (1.40 g, 8.86 mmol) was dissolved in anhydrous Et2O (15 mL). The solution was cooled to −78° C., treated with a 1.6 M solution of n-BuLi (5.53 mL, 8.86 mmol), and stirred for 15 min. The lithium solution was cannulated into a −78° C. solution of 2-fluoro-4-formyl-benzonitrile (Example 1, Step D) in THF (15 mL) and stirred for 15 min. The reaction was quenched with H2O, partitioned between CH2Cl2 and saturated NaHCO3 solution and separated. The aqueous layer was washed with CH2Cl2 (2×), the organic layers combined, dried (Na2SO4), filtered and concentrated to give the title compound after chromatography on SiO2 eluting with 0-3% MeOH/CH2Cl2 w/NH4OH.

Workup

  1. customwas cannulated into a −78° C.
  2. stirringstirred for 15 min
  3. customThe reaction was quenched with H2O
  4. custompartitioned between CH2Cl2 and saturated NaHCO3 solution
  5. customseparated
  6. washThe aqueous layer was washed with CH2Cl2 (2×)
  7. dry with materialdried (Na2SO4)
  8. filtrationfiltered
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-071834415b38447f9242efd1003b1bd0
Source dataset
uspto-grants-2003_02
Patent number
US06525074B2

Reaction notes

Loading…