Methanol → 2-(4-(tert-Butoxycarbonyl)piperazin-1-yl)-5-chlorobenzoic acid
Reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][C:15]=2[C:21]#N)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[OH-:23].[Na+].C[OH:26]>>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][C:15]=2[C:21]([OH:26])=[O:23])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]Participants
4
Conditions
- Temperature
- 80 °C
Procedure
To a solution of 4-(4-chloro-2-cyano-phenyl)-piperazine-1-carboxylic acid tert-butyl ester (0.6 g, 1.86 mmol) in methanol (4.0 mL) was added 1.0 N NaOH (4.0 mL, 4.0 mmol) and the resulting mixture was heated to reflux at 80° C. for 36 h. Additional 1.0 N NaOH (2.0 ml, 2.0 mmol) was added to the reaction mixture and refluxed further for 18 hrs. The reaction mixture was concentrated and acidified to pH 4.0-5.0 using 1.0 N HCl and extracted with chloroform (5×). The combined organics were dried over sodium sulfate, concentrated and dried in vacuo overnight. The product contained approximately 20% amide and was separated after esterification in the next step. ESI-MS m/z: 341(M+1), UV retention time: 2.33 min.
Workup
- temperaturethe resulting mixture was heated
- temperaturerefluxed further for 18 hrs
- concentrationThe reaction mixture was concentrated
- extractionextracted with chloroform (5×)
- dry with materialThe combined organics were dried over sodium sulfate
- concentrationconcentrated
- customdried in vacuo overnight
- customwas separated after esterification in the next step
Sources & evidence
- ORD record
- ord-b9c07a44353a49ec8cec4ea7ecc47ad5
- Source dataset
- uspto-grants-2014_02
- Patent number
- US08653096B2
Reaction notes
Loading…