Boron tribromide → 2,6-Difluoro-3-[4-(3-hydroxy-phenyl)-thiazol-2-ylmethoxy]-benzamide
Reaction equation
[F:1][C:2]1[C:10]([O:11][CH2:12][C:13]2[S:14][CH:15]=[C:16]([C:18]3[CH:23]=[CH:22][CH:21]=[C:20]([O:24]C)[CH:19]=3)[N:17]=2)=[CH:9][CH:8]=[C:7]([F:26])[C:3]=1[C:4]([NH2:6])=[O:5].B(Br)(Br)Br.C([O-])(O)=O.[Na+]>C(Cl)Cl>[F:1][C:2]1[C:10]([O:11][CH2:12][C:13]2[S:14][CH:15]=[C:16]([C:18]3[CH:23]=[CH:22][CH:21]=[C:20]([OH:24])[CH:19]=3)[N:17]=2)=[CH:9][CH:8]=[C:7]([F:26])[C:3]=1[C:4]([NH2:6])=[O:5]Participants
Reactant 3
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 25 °C
Procedure
A solution of 2,6-Difluoro-3-[4-(3-methoxy-phenyl)-thiazol-2-ylmethoxy]-benzamide (0.20 g, 0.53 mmol) in 15 ml of DCM was cooled to −78° C. followed by addition of BBr3 (0.20 ml, 2.14 mmol). The reaction mixture was stirred at 25° C. for 2 h. After the completion of the reaction mixture (TLC monitoring), solution of NaHCO3 (20 mL) was added at 0° C. and extracted with ethyl acetate (3×50 mL). The combined organics was washed with water, brine, dried (Na2SO4), filtered and concentrated. The residue was purified by column chromatography on silica (60-120 M) using ethyl acetate/hexane (50:50) as the eluent to provide the title compound as white solid (0.065 g, 33%). 1H NMR (DMSO-d6, 400 MHz): δ 5.60 (s, 2H), 6.74 (m, 1H), 7.10 (m, 1H), 7.24 (m, 1H), 7.37-7.45 (m, 3H), 7.90 (br s, 1H), 8.10 (s, 1H), 8.17 (br s, 1H) and 9.55 (s, 1H). MS ES+ (362.99), HPLC (method II) Rt=14.95 min.
Workup
- extractionextracted with ethyl acetate (3×50 mL)
- washThe combined organics was washed with water, brine
- dry with materialdried (Na2SO4)
- filtrationfiltered
- concentrationconcentrated
- customThe residue was purified by column chromatography on silica (60-120 M)
Sources & evidence
- ORD record
- ord-703802e4406640a39ac24aaa852c19c7
- Source dataset
- uspto-grants-2012_01
- Patent number
- US08088791B2
Reaction notes
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