Water → 1-acetyl-5-fluoro-2,3-dihydro-3,3-dimethyl-1H-Indole
Reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]([CH2:12][C:13]([CH3:15])=[CH2:14])[C:9](=[O:11])[CH3:10])=[CH:4][CH:3]=1.[Cl-].[Cl-].[Cl-].[Al+3].O>C(OCC)(=O)C>[F:1][C:2]1[CH:3]=[C:4]2[C:5](=[CH:6][CH:7]=1)[N:8]([C:9](=[O:11])[CH3:10])[CH2:12][C:13]2([CH3:15])[CH3:14]Participants
Reactant 3
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 150 °C
Procedure
According to the procedure described in S. Coulton et al. WO9925709 with the following modifications. N-(4-Fluoro-phenyl)-N-(2-methyl-allyl)-acetamide (5 grams, 24.12 mmol) was added to a microwave tube with aluminum trichloride (7 grams, 52.4 mmol). The tube was capped and heated to 150° C. for 20 minutes under microwave. The slurry was worked up with water and ethyl acetate, the organic layer was extracted with 3 washes of saturated sodium bicarbonate solution and the organic layer was dried over magnesium sulfate. The solution was then filtered and rotary evaporated to yield pure 1-(5-Fluoro-3,3-dimethyl-2,3-dihydro-indol-1-yl)-ethanone in quantitative yield. This was converted to the free indoline by suspending the entire 5 grams of product in 20 mL of 6 M HCl and heating in a microwave to 200° C. for 10 minutes. The resulting 5-Fluoro-3,3-dimethyl-2,3-dihydro-1H-indole crystallized on cooling as the hydrochloride salt in quantitative yield. This material was identical to the previously reported compound.
Workup
- customThe tube was capped
- extractionthe organic layer was extracted with 3
- dry with materialof saturated sodium bicarbonate solution and the organic layer was dried over magnesium sulfate
- filtrationThe solution was then filtered
- customrotary evaporated
Sources & evidence
- ORD record
- ord-e1442b980ca14987bec905ca68964d5f
- Source dataset
- uspto-grants-2009_03
- Patent number
- US07501408B2
Reaction notes
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