Hydrochloric Acid → 2-Chloro-3-(5-fluoro-2-methoxy-phenyl)-propionaldehyde

HRID 1971476Notes

Reaction equation

HRID 1971476 reaction equation
N([O-])=O.[Na+].[F:5][C:6]1[CH:7]=[CH:8][C:9]([O:13][CH3:14])=[C:10](N)[CH:11]=1.[CH:15]([CH:17]=[CH2:18])=[O:16].[O-2].[Ca+2].[ClH:21]>O.CC(C)=O>[Cl:21][CH:17]([CH2:18][C:10]1[CH:11]=[C:6]([F:5])[CH:7]=[CH:8][C:9]=1[O:13][CH3:14])[CH:15]=[O:16]

Participants

8

Reactant 5

HCID 313Hydrochloric Acid2×HCID 7847AcroleinHCID 2231055-Fluoro-2-methoxyanilineHCID 6850728CalciumoxideHCID 23668193Sodium Nitrite

Product 1

HCID 580330952-Chloro-3-(5-fluoro-2-methoxy-phenyl)-propionaldehyde

Reagents, catalysts & solvents 2

HCID 180AcetoneSolvent2×HCID 962WaterSolvent

Procedure

A solution of sodium nitrite (36 g, 0.51 mole) in water (50 mL) was slowly added to a solution of 5-fluoro-2-methoxy-phenylamine (61.5 g, 0.48 mol) in hydrochloric acid (20% aqueous solution, 115 mL) at 0° C. After stirring for 10 minutes, a cooled (0° C.) solution of acrolein (50 mL, 0.75 mol) in acetone (100 mL) containing calcium oxide (0.56 g, 0.010 mol) was added slowly to the reaction mixture. This was then followed by a solution of cuprous chloride (5 g, 0.05 mol) in acetone (100 mL) containing hydrochloric acid (20% aqueous solution, 10 mL). The mixture was stirred at 0 to 30° C. for 3 hours, and then extracted three times with dichloromethane (300 mL). The combined organic layers were washed with a saturated aqueous solution of sodium bicarbonate, a saturated aqueous solution of sodium chloride, dried over sodium sulfate, filtered, and evaporated to dryness to give a black viscous oil. The crude product was passed through a short silica column to give the crude product, which was used directly in the next step.

Workup

  1. additionwas added slowly to the reaction mixture
  2. stirringThe mixture was stirred at 0 to 30° C. for 3 hours
  3. extractionextracted three times with dichloromethane (300 mL)
  4. washThe combined organic layers were washed with a saturated aqueous solution of sodium bicarbonate
  5. dry with materiala saturated aqueous solution of sodium chloride, dried over sodium sulfate
  6. filtrationfiltered
  7. customevaporated to dryness
  8. customto give a black viscous oil

Sources & evidence

ORD record
ord-b6760fd97f8b4163b3a513901d9961e7
Source dataset
uspto-grants-2013_04
Patent number
US08431605B2

Reaction notes

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