Acetonitrile → 2-[(2-{2-[2-(Trifluoromethyl)-1,3-thiazol-4-yl]phenoxy}ethyl)amino]ethanol
Reaction equation
Br[CH2:2][CH2:3][O:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[C:11]1[N:12]=[C:13]([C:16]([F:19])([F:18])[F:17])[S:14][CH:15]=1.FC(F)(F)C1SC=C([C:27]2C=CC=C[C:28]=2[OH:33])N=1.BrCCBr.C(#[N:42])C>>[F:17][C:16]([F:19])([F:18])[C:13]1[S:14][CH:15]=[C:11]([C:6]2[CH:7]=[CH:8][CH:9]=[CH:10][C:5]=2[O:4][CH2:3][CH2:2][NH:42][CH2:27][CH2:28][OH:33])[N:12]=1Participants
Conditions
- Temperature
- 70 °C
Procedure
Synthesis of 4-[2-(2-bromoethoxy)phenyl]-2-(trifluoromethyl)-1,3-thiazole (C5) Cesium carbonate (266 mg, 0.816 mmol) was added to a solution of 2-[2-(trifluoromethyl)-1,3-thiazol-4-yl]phenol (C4) (100 mg, 0.408 mmol) and 1,2-dibromoethane (0.35 mL, 4.1 mmol) in acetonitrile (33 mL), and the mixture was heated at 70° C. for 18 hours. After cooling to room temperature, the reaction was partitioned between dichloromethane and water; the organic layer was dried over magnesium sulfate, filtered, and concentrated in vacuo. Purification via silica gel chromatography (Gradient: 10% to 30% ethyl acetate in heptane) afforded the title compound. Yield: 115 mg, 0.327 mmol, 80%. 1H NMR (400 MHz, CDCl3) δ 3.78 (br dd, J=5.5, 5.5 Hz, 2H), 4.48 (dd, J=5.7, 5.5 Hz, 2H), 6.97 (br d, J=8.4 Hz, 1H), 7.13 (ddd, J=7.7, 7.4, 1.1 Hz, 1H), 7.35 (ddd, J=8.3, 7.3, 1.8 Hz, 1H), 8.31 (dd, J=7.8, 1.8 Hz, 1H), 8.37 (s, 1H).
Workup
- temperatureAfter cooling to room temperature
- customthe reaction was partitioned between dichloromethane and water
- dry with materialthe organic layer was dried over magnesium sulfate
- filtrationfiltered
- concentrationconcentrated in vacuo
- customPurification via silica gel chromatography (Gradient: 10% to 30% ethyl acetate in heptane)
Sources & evidence
- ORD record
- ord-2220b755d76f450dae8177de7a461ee1
- Source dataset
- uspto-grants-2014_04
- Patent number
- US08697673B2
Reaction notes
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