Reaction #1904082

Reaction equation

ammonium chloride

1-(2-amino-5-bromophenyl)-2,2,3,3,3-pentafluoropropan-1-one

furan

n-butyllithium

THF

→

N-{4-bromo-2-[2,2,3,3,3-pentafluoro-1-(2-furyl)-1-hydroxypropyl]phenyl}-2-chloroacetamide

Solvents

Ethyl acetate

Conditions

Workup

1. 1
   Temperaturecooled to −78° C.
2. 2
   Temperatureto warm to −30° C.
3. 3
   Temperaturemixture was warmed to rt
4. 4
   Otherorganic layer separated
5. 5
   Dryingdried (MgSO4)
6. 6
   Concentrationconcentrated
7. 7
   workup.DISSOLUTIONThe residue was dissolved in anhydrous THF
8. 8
   TemperatureThe resultant solution was cooled to 0° C.
9. 9
   workup.ADDITIONtreated with triethylamine
10. 10
    workup.ADDITIONfollowed by addition of chloroacetyl chloride following the procedure

Procedure

To a solution of furan (13 g, 190 mmol) in anhydrous THF (150 mL) was added n-butyllithium (2.5 M in hexane, 40 mL, 100 mmol) at 0° C. under nitrogen. The solution was stirred at 0° C. for 30 minutes, cooled to −78° C., and treated with a solution of 1-(2-amino-5-bromophenyl)-2,2,3,3,3-pentafluoropropan-1-one. The mixture was allowed to warm to −30° C., a saturated ammonium chloride solution (100 mL) was added and mixture was warmed to rt. Ethyl acetate (300 mL) was added and organic layer separated, dried (MgSO4), and concentrated. The residue was dissolved in anhydrous THF. The resultant solution was cooled to 0° C., treated with triethylamine followed by addition of chloroacetyl chloride following the procedure described in example 1 to give N-{4-bromo-2-[2,2,3,3,3-pentafluoro-1-(2-furyl)-1-hydroxypropyl]phenyl}-2-chloroacetamide as a white solid. 1H NMR (DMSO-d6): δ 10.54 (s, 1H), 9.11 (s, 1H), 8.18 (d, J=9.0 Hz, 1H), 7.79 (m, 1H), 7.64 (dd, J=8.8, 2.4 Hz, 1H), 7.21 (d, J=1.7 Hz, 1H), 6.71 (s, 1H), 6.58 (m, 1H), 4.35 (d, J=1.5 Hz, 2H). MS (ESI) m/z 462/464 ([M+H]+); MS (ESI) m/z 460/462 ([M−H]−).

Source