p-Anisoyl chloride → 4,5-Dihydro-2-(4-methoxyphenyl)-4,4-dimethyloxazole

HRID 2297397Notes

Reaction equation

HRID 2297397 reaction equation
[NH2:1][C:2]([CH3:6])([CH3:5])[CH2:3][OH:4].[CH3:7][O:8][C:9]1[CH:17]=[CH:16][C:12]([C:13](Cl)=O)=[CH:11][CH:10]=1.S(Cl)(Cl)=O>C(Cl)Cl>[CH3:7][O:8][C:9]1[CH:17]=[CH:16][C:12]([C:13]2[O:4][CH2:3][C:2]([CH3:6])([CH3:5])[N:1]=2)=[CH:11][CH:10]=1

Participants

5

Reactant 3

HCID 7477p-Anisoyl chlorideHCID 118072-Amino-2-methyl-1-propanolHCID 24386Thionyl Chloride

Product 1

HCID 3593374,5-Dihydro-2-(4-methoxyphenyl)-4,4-dimethyloxazoleYield 87.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A solution of 2-amino-2-methyl-propan-1-ol (104.5 g, 1.17 moles) in CH2Cl2 (400 ml) under N2 was dropwise added in 30 minutes with a solution of 4-methoxybenzoyl chloride (100 g, 0.59 moles) in CH2Cl2 (500 ml), keeping the temperature at about 8° C. with water/ice. After 3 hours under stirring the precipitate was filtered over celite and washed with CH2C2. The organic phase was stirred under N2 at 2° C. and dropwise added with thionyl chloride (123 ml, 1.77 moles), keeping the temperature below 10° C. At the end of the dropping the reaction mixture was stirred overnight, then concentrated under vacuum. The residue was taken up in 5% HCl and twice extracted with ethyl ether. The extracts were in turn extracted with 5% HCl. The aqueous phase was alkalinised with concentrated NaOH and extracted three times with ethyl ether, then anhydrified and concentrated under vacuum. The crude was distilled at 95-98° C. (30 Pascal) to give 106.43 g of the title compound (yield: 87.6%).

Workup

  1. customat about 8° C.
  2. filtrationwas filtered over celite
  3. washwashed with CH2C2
  4. stirringThe organic phase was stirred under N2 at 2° C.
  5. customthe temperature below 10° C
  6. stirringAt the end of the dropping the reaction mixture was stirred overnight
  7. concentrationconcentrated under vacuum
  8. extractiontwice extracted with ethyl ether
  9. extractionextracted with 5% HCl
  10. extractionextracted three times with ethyl ether
  11. concentrationconcentrated under vacuum
  12. distillationThe crude was distilled at 95-98° C. (30 Pascal)

Sources & evidence

ORD record
ord-da7d820d426c409f9c2e1791dc61fca6
Source dataset
uspto-grants-2002_12
Patent number
US06492360B1

Reaction notes

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