Cyanamide → 5-(Trifluoromethyl)-1,3-oxazol-2-amine

Temperature

65 °C

5-Trifluoromethyl-oxazol-2-ylamine: The 5-trifluoromethyl-oxazol-2-ylamine, off-white solid and MS: m/e=152.0 (M+), is obtained using the following procedure: To a solution of 21.6 ml (39.4 g, 0.2 mol) of 97% 3-bromo-1,1,1-trifluoroacetone in 40 ml of tert-butanol are added 12.6 g (0.3 mol, 1.5 equiv.) of cyanamide. A slight exotherm is observed. After stirring for 10 min, 19.7 g (0.24 mol, 1.2 equiv.) of finely powdered sodium acetate were added with vigorous stirring and the suspension is heated for 30 min at 65° C., refluxed for 2 h and then allowed to cool. The mixture is poured into a well stirred mixture of 200 ml of ethyl acetate and 100 ml of water. The pH of the aqueous phase is set to ca. 8-9 with 5% sodium bicarbonate solution. The org. phase is separated. The aqueous phase is extracted with 50 ml ethyl acetate. The combined organic phases were washed twice with 20 ml of water and concentrated in vacuo. The residue, 40.2 g, viscous light orange oil, is then purified by flash chromatography on silica gel using a 2:1 mixture of methylene chloride and ethyl acetate as eluent. The fractions containing the desired compound (6.08 g, light yellow oil) and containing more polar impurities were concentrated and repurified by flash chromatography on silica gel using a 98:2 mixture of methylene chloride and methanol as eluant. One obtains 1.83 g (0.012 mol, 6%) of 5-trifluoromethyl-oxazol-2-ylamine.

1. stirringwith vigorous stirring
2. temperaturerefluxed for 2 h
3. temperatureto cool
4. additionThe mixture is poured into a well
5. stirringstirred
6. customphase is separated
7. extractionThe aqueous phase is extracted with 50 ml ethyl acetate
8. washThe combined organic phases were washed twice with 20 ml of water
9. concentrationconcentrated in vacuo
10. customThe residue, 40.2 g, viscous light orange oil, is then purified by flash chromatography on silica gel using
11. additiona 2:1 mixture of methylene chloride and ethyl acetate as eluent
12. additionThe fractions containing the desired compound (6.08 g, light yellow oil) and
13. additioncontaining more polar impurities
14. concentrationwere concentrated
15. customrepurified by flash chromatography on silica gel using
16. additiona 98:2 mixture of methylene chloride and methanol as eluant

ORD record

ord-960408d791794b96bc9b239a50ad6886

Source dataset

uspto-grants-2006_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07119113B2