Water → (S)-2-(2-azidopropyl)-4-fluoro-1-methylbenzene
Reaction equation
CS(O[C@H:6]([CH3:16])[CH2:7][C:8]1[CH:13]=[C:12]([F:14])[CH:11]=[CH:10][C:9]=1[CH3:15])(=O)=O.[N-:17]=[N+:18]=[N-:19].[Na+].O>CN(C=O)C>[N:17]([C@@H:6]([CH3:16])[CH2:7][C:8]1[CH:13]=[C:12]([F:14])[CH:11]=[CH:10][C:9]=1[CH3:15])=[N+:18]=[N-:19]Participants
Conditions
- Temperature
- 80 °C
Procedure
A solution of (R)-1-(5-fluoro-2-methylphenyl)propan-2-yl methanesulfonate (6.3 g, 2.56 mmol) in anhydrous DMF (30 mL) was added sodium azide (3.32 g, 5.11 mmol) and the solution was heated to 80° C. and stirred for 2 h. Then, the temperature was cooled to rt and 20 mL of water was added, extracted with EtOAc/hexane (1/1, v/v), dried over anhydrous MgSO4 and evaporated to give crude oil, which was passed through silicagel pad and evaporated under reduced pressure to give (S)-2-(2-azidopropyl)-4-fluoro-1-methylbenzene (F-3), which used as starting material for next reduction without more purification. To the solution of (S)-2-(2-azidopropyl)-4-fluoro-1-methylbenzene in 80 mL of EtOAc was added Pd/C (500 mg, 10% Pd) and the mixture was hydrogenated under Parr Apparatus (30˜40 psi) for 2 h. The catalyst was removed by filtration through Celite pad, then purified by column chromatography as an eluent (EtOAc/MeOH/NH4OH=93/5/2) to give (S)-1-(5-fluoro-2-methylphenyl)propan-2-amine (F) as pale yellow oil (total yield=30% through 4 steps). MS (ESI) m/z 168.0 [M+H]+; 1H NMR (CDCl3, 500 MHz) δ 7.10 (m, 1H), 6.84 (m, 2H), 3.19 (m, 1H), 2.69 (dd, J=13.5, 6.0 Hz, 1H), 2.56 (dd, J=13.5, 8.0 Hz, 1H), 2.28 (s, 3H), 1.68 (bs, 2H), 1.15 (d, J=6.0 Hz, 3H).
Workup
- temperatureThen, the temperature was cooled to rt
- extractionextracted with EtOAc/hexane (1/1
- dry with materialv/v), dried over anhydrous MgSO4
- customevaporated
- customto give crude oil, which
- customevaporated under reduced pressure
Sources & evidence
- ORD record
- ord-32cbd19ea9db4ae0851a8b14ee20acc6
- Source dataset
- uspto-grants-2014_09
- Patent number
- US08822500B2
Reaction notes
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