Tetrahydrofuran → 3-Chloro-4-(trifluoromethyl)benzaldehyde
Reaction equation
[H-].C([Al+]CC(C)C)C(C)C.[Cl:11][C:12]1[CH:13]=[C:14]([CH:17]=[CH:18][C:19]=1[C:20]([F:23])([F:22])[F:21])[C:15]#N.C1C[O:27]CC1>>[Cl:11][C:12]1[CH:13]=[C:14]([CH:17]=[CH:18][C:19]=1[C:20]([F:23])([F:22])[F:21])[CH:15]=[O:27]Participants
Procedure
Diisobutylaluminum hydride (1.0 M in toluene, 28 mL, 28 mmol) was added slowly via syringe to a solution of 3-chloro-4-(trifluoromethyl)benzonitrile (3.79 g, 18.4 mmol) in THF (50 mL) at 0° C. The reaction was allowed to proceed for 2 hr, then warmed to ambient temperature and stirred an additional 2 hr. The reaction was then cooled to 0° C., and quenched with 3 M aq HCl (75 mL). The mixture was allowed to warm to ambient temperature, and stirred vigorously for 1.5 hr. The mixture was then transferred to a separatory funnel and diluted with Et2O. The separated organic phase was dried over Na2SO4, filtered, and concentrated in vacuo. Flash chromatography (Analogix® Intelliflash 280™; 15% EtOAc/hexanes eluant; SF40-150 g column) yielded 2.84 g (74%) of the title compound as a colorless oil. 1H NMR (300 MHz, DMSO-d6) δ 10.09 (s, 1H), 8.21 (s, 1H), 8.12 (d, J=8.1, 1H), 8.07-8.02 (m, 1H).
Workup
- temperatureThe reaction was then cooled to 0° C.
- customquenched with 3 M aq HCl (75 mL)
- temperatureto warm to ambient temperature
- stirringstirred vigorously for 1.5 hr
- customThe mixture was then transferred to a separatory funnel
- additiondiluted with Et2O
- dry with materialThe separated organic phase was dried over Na2SO4
- filtrationfiltered
- concentrationconcentrated in vacuo
Sources & evidence
- ORD record
- ord-d1c522076ab948218d19f0e95290ef93
- Source dataset
- uspto-grants-2011_08
- Patent number
- US07998993B2
Reaction notes
Loading…