Nitric Acid → [3-nitro-4-(trifluoromethyl)phenyl]methanol

4-(Trifluoromethyl)benzoic acid (15 g, 78.9 mmol) in 90 mL of concentrated sulfuric acid was treated dropwise with a mixture of fuming nitric acid (2 mL) and sulfuric acid (24 mL). The reaction mixture was stirred at ambient temperature for 48 hours and quenched into ice-water. The resulting precipitate (12 g) was collected by filtration, washed with water and dried under reduced pressure. The resulting dry solid (12 g) was dissolved in THF (300 mL), cooled to 0° C., treated with 1M borane-tetrahydrofuran complex (80 mL) and stirred at ambient temperature overnight. Methanol (5 mL) was added dropwise followed by dropwise addition of concentrated HCl (5 mL), refluxed for 1 hour and evaporated to dryness and partitioned between water and diethyl ether. The organic layer was dried over MgSO4 and concentrated under reduced pressure. The residue was chromatographed on silica gel eluting with 30% ethyl acetate hexanes to provide the title compound (3.6 g, 20% yield).

1. customquenched into ice-water
2. filtrationThe resulting precipitate (12 g) was collected by filtration
3. washwashed with water
4. customdried under reduced pressure
5. dry with materialThe resulting dry solid (12 g)
6. dissolutionwas dissolved in THF (300 mL)
7. temperaturecooled to 0° C.
8. additiontreated with 1M borane-tetrahydrofuran complex (80 mL)
9. stirringstirred at ambient temperature overnight
10. additionMethanol (5 mL) was added dropwise
11. additionfollowed by dropwise addition of concentrated HCl (5 mL)
12. temperaturerefluxed for 1 hour
13. customevaporated to dryness
14. custompartitioned between water and diethyl ether
15. dry with materialThe organic layer was dried over MgSO4
16. concentrationconcentrated under reduced pressure
17. customThe residue was chromatographed on silica gel eluting with 30% ethyl acetate hexanes

ORD record

ord-a6a8cc39c15747ec98647d7c467abed8

Source dataset

uspto-grants-2003_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06632418B2