Hydrogen Bromide → 4-Bromo-3-fluoro-2-methylaniline
Reaction equation
[F:1][C:2]1[C:3]([CH3:9])=[C:4]([CH:6]=[CH:7][CH:8]=1)[NH2:5].[BrH:10].[OH-].[Na+].C(=O)(O)[O-].[Na+]>C(O)(=O)C.CCCCCC.C(OCC)(=O)C.CS(C)=O>[Br:10][C:8]1[CH:7]=[CH:6][C:4]([NH2:5])=[C:3]([CH3:9])[C:2]=1[F:1]Participants
Reactant 4
Product 1
Reagents, catalysts & solvents 4
Conditions
- Temperature
- 10 °C
Procedure
To a stirred solution of 3-fluoro-2-methylaniline (25 g, 200 mmol) in acetic acid (140 mL) at 0-5° C. was added hydrogen bromide (100 mL, 200 mmol) then dimethyl sulfoxide (72 mL) was added slowly dropwise (reaction is exothermic and at temperature higher than 5-15° C. produces dibromoisomer). The mixture was stirred at 5-15° C. for 12 h (mixture became clear solution). The resulting solution was cooled to 0° C. and neutralized with sodium hydroxide then with sodium bicarbonate to pH 7. The mixture was extracted with ethyl acetate. The organic layer was concentrated under reduced pressure. Flash chromatography (0-10% ethyl acetate in hexane) gave the desired product as a white solid (23.3 g, 114 mmol, 57% yield). 1H NMR (400 MHz, CHLOROFORM-d) δ (ppm) 7.11 (t, J=8.20 Hz, 1H), 6.35 (d, J=8.98 Hz, 1H), 3.72 (br. s., 2H), 2.07 (d, J=1.95 Hz, 3H).
Workup
- custom(reaction is exothermic and at temperature higher than 5-15° C. produces dibromoisomer)
- extractionThe mixture was extracted with ethyl acetate
- concentrationThe organic layer was concentrated under reduced pressure
Sources & evidence
- ORD record
- ord-d458b6ea075e4e24a7fb9d2c67bdeace
- Source dataset
- uspto-grants-2013_08
- Patent number
- US08507492B2
Reaction notes
Loading…