Toluene → 4-(4-Chloromethylphenoxy)methyl-5-methyl-2-phenyloxazole

HRID 1059093Notes

Reaction equation

HRID 1059093 reaction equation
[CH3:1][C:2]1[O:6][C:5]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)=[N:4][C:3]=1[CH2:13][O:14][C:15]1[CH:20]=[CH:19][C:18]([CH2:21]O)=[CH:17][CH:16]=1.O1CCCC1.C1(C)C=CC=CC=1.S(Cl)([Cl:37])=O>[Cl-].[Na+].O>[Cl:37][CH2:21][C:18]1[CH:19]=[CH:20][C:15]([O:14][CH2:13][C:3]2[N:4]=[C:5]([C:7]3[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=3)[O:6][C:2]=2[CH3:1])=[CH:16][CH:17]=1

Participants

6

Reactant 4

HCID 1140TolueneHCID 8028TetrahydrofuranHCID 24386Thionyl ChlorideHCID 110228074-(5-Methyl-2-phenyl-4-oxazolylmethoxy)benzyl alcohol

Product 1

HCID 109469404-(4-Chloromethylphenoxy)methyl-5-methyl-2-phenyloxazoleYield 87.9%

Reagents, catalysts & solvents 1

HCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
5 °C

Procedure

{4-[(5-Methyl-2-phenyl-1,3-oxazol-4-yl)methoxy]phenyl}-methanol (300 g), tetrahydrofuran (750 ml) and toluene (750 ml) were charged and the mixture was cooled to 5° C. Thionyl chloride (88 ml) was added dropwise at not higher than 15° C. over 10 min and the mixture was reacted at 10-15° C. for 1 hr. 10% Brine (900 ml) was added dropwise at the same temperature over about 10 min, and the mixture was stood for 30 min, partitioned and activated carbon (15 g) was added to the organic layer. The mixture was stirred for about 1 hr, and the activated carbon was filtered off and the mixture was washed with toluene (300 ml). The organic layer was concentrated to about 805 g and then heated to about 60° C. to dissolve crystals, followed by standing for cooling. The mixture was cooled to about 25° C. over 30 min and n-hexane (1800 ml) was added dropwise over about 30 min. The mixture was cooled to around 5° C. and aged for 1 hr. The crystals were collected by filtration and washed with cold toluene-n-hexane (1:3) (600 ml). The crystals were dried under reduced pressure at 40° C. to give pale-yellow 4-{[4-(chloromethyl)phenoxy]methyl}-5-methyl-2-phenyl-1,3-oxazole (280.0 g) in a yield of 87.9%.

Workup

  1. customthe mixture was reacted at 10-15° C. for 1 hr
  2. custompartitioned
  3. additionactivated carbon (15 g) was added to the organic layer
  4. filtrationthe activated carbon was filtered off
  5. washthe mixture was washed with toluene (300 ml)
  6. concentrationThe organic layer was concentrated to about 805 g
  7. temperatureheated to about 60° C.
  8. dissolutionto dissolve crystals
  9. temperaturefor cooling
  10. temperatureThe mixture was cooled to about 25° C. over 30 min
  11. additionn-hexane (1800 ml) was added dropwise over about 30 min
  12. temperatureThe mixture was cooled to around 5° C. and aged for 1 hr
  13. filtrationThe crystals were collected by filtration
  14. washwashed with cold toluene-n-hexane (1:3) (600 ml)
  15. customThe crystals were dried under reduced pressure at 40° C.

Sources & evidence

ORD record
ord-aa311a5dd8684077a66a20729fa9a404
Source dataset
uspto-grants-2003_02
Patent number
US06518435B1

Reaction notes

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