Dimethylformamide → HCID 18518301, compound

HRID 2299192Notes

Reaction equation

HRID 2299192 reaction equation
[CH2:1]([C:8]1[CH:13]=[C:12]([O:14][CH3:15])[CH:11]=[CH:10][C:9]=1[CH2:16][C:17]([OH:19])=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CN(C=O)C.C(Cl)(=O)C(Cl)=O.[Al+3].[Cl-].[Cl-].[Cl-]>C(Cl)Cl>[CH3:15][O:14][C:12]1[CH:11]=[CH:10][C:9]2[CH2:16][C:17](=[O:19])[C:7]3[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=3[CH2:1][C:8]=2[CH:13]=1

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 65578Oxalyl chloride2×HCID 6451240Aluminum(III) ChlorideHCID 12743495HCID 12743495, compound

Product 1

HCID 18518301HCID 18518301, compoundYield 92%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Procedure

A solution of 2-benzyl-4methoxyphenylacetic acid (215 g of crude material that contained 204.6 g (0.80 mole) of pure material) in CH2Cl2 (1 L) was stirred under argon at ambient temperature, and DMF (1 mL) was added, followed by oxalyl chloride (400 mL, 4.59 mole). The oxalyl chloride was added over 1 hr, dropwise initially to control the vigorous gas evolution. The solution was stirred for 16 h at ambient temperature and then was concentrated to give the crude acid chloride (207.7 g, 0.756 mol, 95%) as a yellow liquid. This liquid was dissolved in CH2Cl2 to a total volume of 500 mL, and the solution and AlCl3 (100.8 g, 0.756 mol) were added concurrently over 1 hr to CH2Cl2 (3.7 L) with stirring under argon at ambient temperature. The temperature was 28° C. at the completion of the addition. The reaction mixture was stirred for 16 h at ambient temperature, during which time a solid precipitated. H2O (1 L) was added, initially dropwise, over a period of 30 min. The mixture was then separated and the organic phase was washed sequentially with H2O (1 L) and 5% aqueous NaHCO3 (1 L). The CH2Cl2 solution was then concentrated to give a yellow solid (175.3 g). Recrystallization from EtOAc/hexane gave the title compound (128 g, 71%): mp 107-109° C.

Workup

  1. concentrationwas concentrated
  2. customto give the crude acid chloride (207.7 g, 0.756 mol, 95%) as a yellow liquid
  3. stirringwith stirring under argon at ambient temperature
  4. additionThe temperature was 28° C. at the completion of the addition
  5. stirringThe reaction mixture was stirred for 16 h at ambient temperature, during which time a solid
  6. customprecipitated
  7. additionH2O (1 L) was added
  8. waitinitially dropwise, over a period of 30 min
  9. customThe mixture was then separated
  10. washthe organic phase was washed sequentially with H2O (1 L) and 5% aqueous NaHCO3 (1 L)
  11. concentrationThe CH2Cl2 solution was then concentrated

Sources & evidence

ORD record
ord-5b4cda33431b4ec8baafe8ca0afb78e7
Source dataset
uspto-grants-2002_12
Patent number
US06495560B1

Reaction notes

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