Sulfuric Acid → N-(1-(4-Chloro-3-fluorophenyl)-2-methylpropan-2-YL)acetamide
Reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]([CH3:12])(O)[CH3:10])=[CH:4][C:3]=1[F:13].[C:14](#[N:16])[CH3:15].S(=O)(=O)(O)[OH:18].[OH-].[Na+]>C(O)(=O)C>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]([NH:16][C:14](=[O:18])[CH3:15])([CH3:12])[CH3:10])=[CH:4][C:3]=1[F:13]Participants
Conditions
- Temperature
- 65 °C
Procedure
To a mixture of 1-(4-chloro-3-fluorophenyl)-2-methylpropan-2-ol (8.61 g, 42.50 mmol), acetonitrile (13 mL, 255.0 mmol) and acetic acid (80 mL) was added sulfuric acid (13 mL) dropwise and the mixture was heated at 65° C. for 5 h. The mixture was cooled to rt and poured into ice water (400 mL) and the resulting mixture was adjusted to pH>11 with NaOH, and extracted with EtOAc (150 mL×3). The combined organic phases were washed with brine (150 mL×2), dried over anhydrous Na2SO4 (40 g) and filtered. The filtrate was concentrated in vacuo. The residue was purified by a silica gel column chromatography (PE/EtOAc (V/V)=2:1) to give the title compound as a yellow solid (4.38 g, 42.1%). The compound was characterized by the following spectroscopic data:
Workup
- temperatureThe mixture was cooled to rt
- extractionextracted with EtOAc (150 mL×3)
- washThe combined organic phases were washed with brine (150 mL×2)
- dry with materialdried over anhydrous Na2SO4 (40 g)
- filtrationfiltered
- concentrationThe filtrate was concentrated in vacuo
- customThe residue was purified by a silica gel column chromatography (PE/EtOAc (V/V)=2:1)
Sources & evidence
- ORD record
- ord-b8f7e2d2c8e04761a8667f1d3862adcf
- Source dataset
- uspto-grants-2016_09
- Patent number
- US09434695B2
Reaction notes
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