Dimethylamine → 2-[(Dimethylamino)methyl]-3,4,5-trifluorophenol

HRID 1071215Notes

Reaction equation

HRID 1071215 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([OH:10])[CH:5]=[C:6]([F:9])[C:7]=1[F:8].[CH2:11]=O.O.ClCCl.[CH3:17][NH:18][CH3:19]>>[OH:10][C:4]1[C:3]([CH2:17][N:18]([CH3:11])[CH3:19])=[C:2]([F:1])[C:7]([F:8])=[C:6]([F:9])[CH:5]=1

Participants

6

Reactant 5

HCID 674DimethylamineHCID 712FormaldehydeHCID 962WaterHCID 6344DichloromethaneHCID 27779433,4,5-Trifluorophenol

Product 1

HCID 102420362-[(Dimethylamino)methyl]-3,4,5-trifluorophenol

Conditions

Temperature
0 °C

Procedure

400 g of 3,4,5-trifluorophenol are initially charged in 359 ml of 40% aqueous dimethylamine solution and cooled to 0° C. At 0-5° C., 243 ml of 37% aqueous formaldehyde solution are added dropwise within 90 min. Subsequently, the mixture is stirred at room temperature for 20 hours. The mixture is admixed with 600 ml of water and 500 ml of dichloromethane. The organic phase is removed, the aqueous phase is extracted once with dichloromethane, the combined organic phases are dried and the solvent is distilled off under reduced pressure. The crude product is taken up in 500 ml of water and adjusted to pH 1-2 with cooling in an ice bath using dilute hydrochloric acid. The acidic solution is extracted once with dichloromethane and subsequently adjusted to pH 8-9 with cooling in an ice bath using dilute sodium hydroxide solution. The alkaline reaction solution is extracted three times with dichloromethane, the combined organic phases are washed once with water and dried, and the solvent is removed under reduced pressure. The crude product is subsequently fractionally distilled under reduced pressure. 305 g (55% of theory) of a light yellow liquid having a boiling point of 96° C. at 10 mbar are obtained.

Workup

  1. customThe organic phase is removed
  2. extractionthe aqueous phase is extracted once with dichloromethane
  3. customthe combined organic phases are dried
  4. distillationthe solvent is distilled off under reduced pressure
  5. temperaturewith cooling in an ice bath
  6. extractionThe acidic solution is extracted once with dichloromethane
  7. temperaturewith cooling in an ice bath
  8. customThe alkaline reaction solution
  9. extractionis extracted three times with dichloromethane
  10. washthe combined organic phases are washed once with water
  11. customdried
  12. customthe solvent is removed under reduced pressure
  13. distillationThe crude product is subsequently fractionally distilled under reduced pressure
  14. customare obtained

Sources & evidence

ORD record
ord-67952cb0dc4d46bc9971dc50958c5d8f
Source dataset
uspto-grants-2005_06
Patent number
US06903239B2

Reaction notes

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