p-Fluoronitrobenzene → HCID 66580012, compound

Temperature

0 °C

Sodium hydride (55%, 3.22 g) was added to DMF (20 mL) and the mixture was cooled to 0° C. Then, (R)-1,1,1-trifluoro-2-propanol (8.5 g) [CAS 17628-73-8] was added over a period of 1 h and stirring was continued for 30 minutes at 0° C. A solution of 1-fluoro-4-nitro-benzene [CAS 350-46-9] (10 g) in DMF (15 mL) was added over a period of 1.5 h while the internal temperature was kept between 5 to 15° C. Following addition, the mixture was allowed to warm to RT and stirring was continued for another 12 h. The reaction mixture was acidified and partitioned between ethyl acetate and water. The organic layer was separated, dried over Na2SO4 and evaporated to dryness. The residue was dissolved in methanol (150 ml) and Pd on carbon (10% Pd, 1 g) was added. The mixture was then hydrogenated at RT for 12 hours. The catalyst was removed by filtration and the filtrate was concentrated in vacuo to provide crude 4-((R)-2,2,2-trifluoro-1-methyl-ethoxy)-phenylamine as a dark liquid (14.5 g). MS (m/e): 206.1 (MH+).

1. customwas kept between 5 to 15° C
2. additionaddition
3. temperatureto warm to RT
4. stirringstirring
5. waitwas continued for another 12 h
6. custompartitioned between ethyl acetate and water
7. customThe organic layer was separated
8. dry with materialdried over Na2SO4
9. customevaporated to dryness
10. dissolutionThe residue was dissolved in methanol (150 ml)
11. additionPd on carbon (10% Pd, 1 g) was added
12. waitThe mixture was then hydrogenated at RT for 12 hours
13. customThe catalyst was removed by filtration
14. concentrationthe filtrate was concentrated in vacuo

ORD record

ord-fa5262dd95644a3ab888f93fe6d33e70

Source dataset

uspto-grants-2014_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08703807B2