Reaction #1121796

Reaction equation

NH4Cl

3-bromo-1,1-dimethoxy-propane

2-chloro-5-fluoro-pyridine-4-carbaldehyde

iodine

→

1-(2-chloro-5-fluoro-pyridin-4-yl)-4,4-dimethoxy-butan-1-ol

Yield 25.0%

Solvents

water

THF

THF

THF

Conditions

Workup

1. 1
   workup.STIRRINGThe mixture is stirred at this temperature for 2 hours
2. 2
   TemperatureThen the reaction mixture is cooled in an ice bath
3. 3
   Extractionthe mixture is extracted with EtOAc
4. 4
   WashThe combined organic layers are washed with brine
5. 5
   Dryingdried over Na2SO4
6. 6
   Filtrationfiltered
7. 7
   Concentrationconcentrated down
8. 8
   OtherThe crude product is purified by chromatography (EtOAc/hexane: 10%˜40%)

Procedure

To a solution of Mg (0.71 g, 30 mmol) in THF (10 mL) are added cat. iodine and a solution of 3-bromo-1,1-dimethoxy-propane (3.99 g, 21.57 mmol) in THF (10 mL). The mixture is stirred at room temperature for 2 hours. At −30° C., to a solution of 2-chloro-5-fluoro-pyridine-4-carbaldehyde (2.0 g, 12.54 mmol) in THF (5 mL) is added to the above prepared Grignard reagent. The mixture is stirred at this temperature for 2 hours. Then the reaction mixture is cooled in an ice bath, saturated NH4Cl and water are added and the mixture is extracted with EtOAc. The combined organic layers are washed with brine, dried over Na2SO4, filtered and concentrated down. The crude product is purified by chromatography (EtOAc/hexane: 10%˜40%) to give 1-(2-chloro-5-fluoro-pyridin-4-yl)-4,4-dimethoxy-butan-1-ol (0.81 g, 25%). M/Z=264.13[M+1]

Source