Sodium Carbonate → HCID 59438535, compound

Temperature

80 °C

To a solution of 24.98 g (113 mmol) 4-(trifluoromethyl)-2-methoxy-benzoic acid in 220 ml toluene were added 82 ml (1.13 mol) thionyl chloride and 5 drops dimethylformamide. The mixture was heated to 80° C. for 3 h. Then the reaction mixture was concentrated at 50° C./10 mbar. The remaining acid chloride, 27.9 g of a light yellow liquid, was dissolved in 160 ml dichloromethane, cooled to 0° C. and a solution of 20.34 g (228 mmol) 2-amino-2-methyl-propan-1-ol in 60 ml dichloromethane added. The mixture was allowed to stir at ambient temperature for 16 h. The off-white suspension was diluted with water, the aqueous phase evaporated and the organic phase extracted 3 times with ethyl acetate. The combined organic layers were dried over Na2SO4, filtered and concentrated. The crude product, 33.2 g N-(2-hydroxy-1,1-dimethyl-ethyl)-2-methoxy-4-trifluoro-methyl-benzamide, a light yellow oil was dissolved in 220 ml dichloromethane and cooled to 0° C. Then 24.7 ml (340 mmol) thionyl chloride was added drop-wise and the resulting light yellow solution stirred at ambient temperature for 16 h. Then the pH was adjusted to 10 by addition of saturated aqueous Na2CO3 solution. The aqueous layer was separated and extracted 3 times with tert-butyl methyl ether. The combined organic phases were washed twice with brine, dried over Na2SO4, filtered and concentrated. 2-(2-Methoxy-4-trifluoromethyl-phenyl)-4,4-dimethyl-4,5-dihydro-oxazole was obtained as light yellow oil which was used without further purification: MS (ISP): 274.1 ((M+H)+.).

1. concentrationThen the reaction mixture was concentrated at 50° C./10 mbar
2. dissolutionThe remaining acid chloride, 27.9 g of a light yellow liquid, was dissolved in 160 ml dichloromethane
3. temperaturecooled to 0° C.
4. customthe aqueous phase evaporated
5. extractionthe organic phase extracted 3 times with ethyl acetate
6. dry with materialThe combined organic layers were dried over Na2SO4
7. filtrationfiltered
8. concentrationconcentrated
9. dissolutionThe crude product, 33.2 g N-(2-hydroxy-1,1-dimethyl-ethyl)-2-methoxy-4-trifluoro-methyl-benzamide, a light yellow oil was dissolved in 220 ml dichloromethane
10. temperaturecooled to 0° C
11. stirringthe resulting light yellow solution stirred at ambient temperature for 16 h
12. customThe aqueous layer was separated
13. extractionextracted 3 times with tert-butyl methyl ether
14. washThe combined organic phases were washed twice with brine
15. dry with materialdried over Na2SO4
16. filtrationfiltered
17. concentrationconcentrated

ORD record

ord-74dbcf1874644957a475aabfcdebe845

Source dataset

uspto-grants-2011_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08080541B2