Dimethyl Sulfoxide → 4-(2-Chloroethoxy)-5-methoxyphthalaldehyde

HRID 989352Notes

Reaction equation

HRID 989352 reaction equation
C(Cl)(=O)C(Cl)=O.CS(C)=O.[Cl:11][CH2:12][CH2:13][O:14][C:15]1[C:20]([O:21][CH3:22])=[CH:19][C:18]([CH2:23][OH:24])=[C:17]([CH2:25][OH:26])[CH:16]=1.C(N(CC)CC)C>C(Cl)Cl.CO>[Cl:11][CH2:12][CH2:13][O:14][C:15]1[CH:16]=[C:17]([CH:25]=[O:26])[C:18](=[CH:19][C:20]=1[O:21][CH3:22])[CH:23]=[O:24]

Participants

7

Reactant 4

HCID 679Dimethyl Sulfoxide2×HCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 11630152[4-(2-Chloroethoxy)-2-(hydroxymethyl)-5-methoxyphenyl]methanol

Product 1

HCID 116944184-(2-Chloroethoxy)-5-methoxyphthalaldehydeYield 65.6%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent3×

Conditions

Temperature
-78 °C

Procedure

To a 500 mL 3-neck round bottom flask fitted with mechanical stirrer, thermometer and addition funnel is added 100 mL dry methylene chloride and 8 mL of oxalyl chloride under nitrogen. This is cooled to −78° C. in a dry ice/acetone bath, then 13.6 mL DMSO in 25 mL dry methylene chloride is added dropwise. After complete addition it is further stirred for 5 minutes. Then 9.87 g of [4-(2-chloroethoxy)-2-(hydroxymethyl)-5-methoxyphenyl]methanol in 10 mL of dry methylene chloride (with enough DMSO added to dissolve the solid) is added dropwise. The reaction mixture is stirred for an additional 30 minutes, then 100 mL of triethylamine is added slowly at −78° C. The solution is stirred for 10 minutes, allowed to warm to room temperature and then 200 mL of ice/water is added. The aqueous layer is extracted with methylene chloride (2×100 mL). The organic layer is dried over MgSO4, filtered and evaporated to give the crude product as a solid. This solid is slurried with cold methanol and filtered, washed with cold methanol, then dried to give 6.37 g of 4-(2-chloroethoxy)-5-methoxyphthalaldehyde as a yellowish solid, m.p. 113-4° C.

Workup

  1. customTo a 500 mL 3-neck round bottom flask fitted with mechanical stirrer
  2. additionthermometer and addition funnel
  3. additionAfter complete addition it
  4. dissolutionto dissolve the solid)
  5. additionis added dropwise
  6. stirringThe reaction mixture is stirred for an additional 30 minutes
  7. stirringThe solution is stirred for 10 minutes
  8. temperatureto warm to room temperature
  9. extractionThe aqueous layer is extracted with methylene chloride (2×100 mL)
  10. dry with materialThe organic layer is dried over MgSO4
  11. filtrationfiltered
  12. customevaporated
  13. customto give the crude product as a solid
  14. filtrationfiltered
  15. washwashed with cold methanol
  16. customdried

Sources & evidence

ORD record
ord-cc5fde04f2dc4cc2aba9c54cb0c8414e
Source dataset
uspto-grants-2003_10
Patent number
US06638929B2

Reaction notes

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