1-(5-Chloro-2,3-dimethoxyphenyl)ethanol → 1-(5-Chloro-2,3-dimethoxyphenyl)ethanone

HRID 1910646Notes

Reaction equation

HRID 1910646 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([O:13][CH3:14])[C:5]([O:11][CH3:12])=[C:6]([CH:8]([OH:10])[CH3:9])[CH:7]=1.C1C=C[NH+]=CC=1.[O-][Cr](Cl)(=O)=O>C(Cl)Cl.CC(OC)(C)C>[Cl:1][C:2]1[CH:3]=[C:4]([O:13][CH3:14])[C:5]([O:11][CH3:12])=[C:6]([C:8](=[O:10])[CH3:9])[CH:7]=1

Participants

5

Reactant 2

HCID 140929151-(5-Chloro-2,3-dimethoxyphenyl)ethanolHCID 178418287HCID 178418287, compound4×

Product 1

HCID 140929161-(5-Chloro-2,3-dimethoxyphenyl)ethanoneYield 72%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent3×HCID 15413tert-Butyl methyl etherSolvent2×

Procedure

1-(5-Chloro-2,3-dimethoxy-phenyl)-ethanol (204 g, 943 mmol) was dissolved in DCM (2.0 L) and PCC (was added to the reaction mixture in portions, over 2 hours. Over the first 1.5 hours the temperature increased from 17.2° C. to 30.7° C. while a total of 315 g PCC was added. Addition of the remaining PCC did not result in a temperature increase. The reaction mixture was tested by TLC 1 hour after the PCC addition was completed; full conversion was observed. After an additional 40 min, 2 L TBME was added and a 4° C. exotherm was observed. The dark slurry was poured into 0.2 kg celite, mixed, then filtered over an additional 0.2 kg celite. The tar-like material remained in the reaction flask. DCM/TBME solution was concentrated under reduced pressure. A coating of tar formed on the flask walls; a solid also formed. The solid was dissolved in 0.2 L DCM (the tar did not dissolve). The solution was mixed with 0.2 kg silica gel and the DCM was allowed to evaporate. The product pre-adsorbed on silica gel was placed on top of a silica gel plug (0.4 kg silica gel) and the organic material was eluted with TBME until no product was observed by TLC. The resulting yellow solution was concentrated to yield a yellow solid. This solid was re-dissolved in TBME and the solution was flushed through a 0.4 kg silica gel plug. The resulting solution was concentrated to yield 145.8 g dry solid (72% yield, 95% pure by HPLC).

Workup

  1. additionwas added
  2. customdid not result in a temperature
  3. temperatureincrease
  4. customwas tested by TLC 1 hour
  5. additionThe dark slurry was poured into 0.2 kg celite
  6. additionmixed
  7. filtrationfiltered over an additional 0.2 kg celite
  8. concentrationDCM/TBME solution was concentrated under reduced pressure
  9. customA coating of tar formed on the flask walls
  10. customa solid also formed
  11. dissolutiondid not dissolve)
  12. additionThe solution was mixed with 0.2 kg silica gel
  13. customto evaporate
  14. washthe organic material was eluted with TBME until no product
  15. concentrationThe resulting yellow solution was concentrated
  16. customto yield a yellow solid
  17. customthe solution was flushed through a 0.4 kg silica gel plug
  18. concentrationThe resulting solution was concentrated
  19. customto yield 145.8 g
  20. customdry solid (72% yield, 95% pure by HPLC)

Sources & evidence

ORD record
ord-0bac4a9707bb4f02903d85f152188c40
Source dataset
uspto-grants-2013_12
Patent number
US08604021B2

Reaction notes

Loading…