Benzoyl Peroxide → HCID 58138932, compound

In a 500 mL round-bottomed flask N-(4-cyano-2-methylphenyl)-2,2,2-trifluoroacetamide (Intermediate 1; 7.3 g, 32.0 mmol), NBS (5.98 g, 33.6 mmol), and benzoyl peroxide (70%) (1.162 g, 4.80 mmol) were added to carbon tetrachloride (150 mL). The reaction mixture was then heated to reflux under argon for 4 days. The reaction mixture was cooled to room temperature then NBS (0.5 eq, 3 g) and benzoyl peroxide (0.075 eq, 0.581 g) were added. The reaction mixture was then heated to reflux for a further 18 hrs. The reaction mixture was allowed to cool to room temperature then poured into 2M NaOH (100 mL). The organic layer was collected then washed with a solution of sodium metabisulfite (10 g in 100 mL water), dried (MgSO4), filtered and the solvent removed. The resulting orange oil was then purified through a plug of silica gel eluting with 1-10% EtOAc:isoHexane. The desired fractions were then combined and evaporated to dryness to give a 1:1 mixture of the title compound and the starting material as an orange solid (9 g) which was then used in the next step without further purification.

1. temperatureThe reaction mixture was then heated
2. temperatureto reflux under argon for 4 days
3. temperatureThe reaction mixture was then heated
4. temperatureto reflux for a further 18 hrs
5. temperatureto cool to room temperature
6. customThe organic layer was collected
7. washthen washed with a solution of sodium metabisulfite (10 g in 100 mL water)
8. dry with materialdried (MgSO4)
9. filtrationfiltered
10. customthe solvent removed
11. customThe resulting orange oil was then purified through a plug of silica gel eluting with 1-10% EtOAc
12. customevaporated to dryness
13. customto give

ORD record

ord-1568f710ff2345878262483069a596ab

Source dataset

uspto-grants-2012_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08283365B2