Trifluoroacetic acid → 2-Chloro-5-(difluoromethyl)-3-(4-(oxetan-3-yl)piperazin-1-yl)aniline
Reaction equation
C1(OC)C=CC=CC=1.[Cl:9][C:10]1[C:15]([N:16]2[CH2:21][CH2:20][N:19]([CH:22]3[CH2:25][O:24][CH2:23]3)[CH2:18][CH2:17]2)=[CH:14][C:13]([CH:26]([F:28])[F:27])=[CH:12][C:11]=1[N:29](CC1C=CC(OC)=CC=1)C(=O)OC(C)(C)C.C(O)(C(F)(F)F)=O>ClCCCl>[Cl:9][C:10]1[C:15]([N:16]2[CH2:17][CH2:18][N:19]([CH:22]3[CH2:25][O:24][CH2:23]3)[CH2:20][CH2:21]2)=[CH:14][C:13]([CH:26]([F:28])[F:27])=[CH:12][C:11]=1[NH2:29]Participants
5
Reactant 3
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 60 °C
Procedure
Anisole (633 μl, 5.80 mmol) was added to a solution of tert-butyl (2-chloro-5-(difluoromethyl)-3-(4-(oxetan-3-yl)piperazin-1-yl)phenyl)(4-methoxybenzyl)carbamate (312 mg, 0.58 mmol) in DCE (3 mL), followed by the addition 2.8 mL of TFA. The reaction was stirred at 60° C. for 3 h. The residue was partitioned between CH2Cl2 and sat. NaHCO3, and extracted into CH2Cl2 (3×). The solution was dried over Na2SO4 and concentrated. The residue was dissolved in MeOH and loaded onto a 5 g Strata SCX ion exchange cartridge, washing with MeOH. The desired product was eluted with 7 N NH3—CH3OH. After concentration, 163.4 mg of 2-chloro-5-(difluoromethyl)-3-(4-(oxetan-3-yl)piperazin-1-yl)aniline was obtained.
Workup
- customThe residue was partitioned between CH2Cl2 and sat. NaHCO3
- extractionextracted into CH2Cl2 (3×)
- dry with materialThe solution was dried over Na2SO4
- concentrationconcentrated
- dissolutionThe residue was dissolved in MeOH
- washwashing with MeOH
- washThe desired product was eluted with 7 N NH3—CH3OH
- concentrationAfter concentration
Sources & evidence
- ORD record
- ord-88307b3ae42c4a14a47fd8fbc5ca46c3
- Source dataset
- uspto-grants-2016_03
- Patent number
- US09273057B2
Reaction notes
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