Dimethyl Sulfoxide → (S)-2-methyl-3-[4-(4-trifluoromethyl-phenyl)-piperazin-1-yl]-propionaldehyde
Reaction equation
C(Cl)(=O)C(Cl)=O.CS(C)=O.[CH3:11][C@@H:12]([CH2:15][N:16]1[CH2:21][CH2:20][N:19]([C:22]2[CH:27]=[CH:26][C:25]([C:28]([F:31])([F:30])[F:29])=[CH:24][CH:23]=2)[CH2:18][CH2:17]1)[CH2:13][OH:14].C(N(CC)CC)C>ClCCl.O>[CH3:11][C@@H:12]([CH2:15][N:16]1[CH2:21][CH2:20][N:19]([C:22]2[CH:27]=[CH:26][C:25]([C:28]([F:30])([F:29])[F:31])=[CH:24][CH:23]=2)[CH2:18][CH2:17]1)[CH:13]=[O:14]Participants
Reactant 4
Product 1
Reagents, catalysts & solvents 2
Conditions
- Temperature
- -70 °C
Procedure
A 2 M solution of oxalyl dichloride in dichloromethane (4.96 mL; 13.2 mmol) is diluted with dichloromethane (35 mL); is cooled to −70° C. and dimethylsulfoxide (0.94 mL; 13.2 mmol) is added. The resulting mixture is stirred for 20 minutes. The temperature is allowed to reach −60° C. and a solution of (S)-2-methyl-3-[4-(4-trifluoromethyl-phenyl)-piperazin-1-yl]-propan-1-ol (2.0 g; 6.6 mmol, prepared in accordance with Example 65) in dichloromethane (20 mL) is added over 5 minutes. The resulting mixture is stirred at −60° C. for 2 hours before triethylamine (4.61 mL; 33.1 mmol) is added. After 10 minutes reaction time, the reaction mixture is allowed to slowly reach room temperature. The reaction is treated with water (100 mL), the organic layer is separated and is washed with water (2×100 mL) and concentrated to afford the desired product (1.99 g; 6.6 mmol). The crude product is engaged in the next step without further purification.
Workup
- customto reach −60° C.
- additionis added
- customAfter 10 minutes reaction time
- customis allowed to slowly reach room temperature
- customthe organic layer is separated
- washis washed with water (2×100 mL)
- concentrationconcentrated
Sources & evidence
- ORD record
- ord-d826a61fb7b54dd6a4bcc392b14fe800
- Source dataset
- uspto-grants-2015_08
- Patent number
- US09096524B2
Reaction notes
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