Hydrochloric Acid → 4-fluoro-2-methyl-2,3-dihydro-1H-indole
Reaction equation
Cl.C(O[C@H](C)C([N:13]1[C:21]2[C:16](=[C:17]([F:22])[CH:18]=[CH:19][CH:20]=2)[CH2:15][CH:14]1[CH3:23])=O)C1C=CC=CC=1.ClC1N=C(Cl)C=C(OC)N=1>C(O)C>[F:22][C:17]1[CH:18]=[CH:19][CH:20]=[C:21]2[C:16]=1[CH2:15][CH:14]([CH3:23])[NH:13]2Participants
Procedure
8.2 ml of concentrated hydrochloric acid are added to a solution of 1.69 g of (R)-2-benzyloxy-1-(4-fluoro-2-methyl-2,3-dihydroindol-1-yl)propan-1-one diastereoisomer (2) in 200 ml of absolute ethanol. The reaction mixture is refluxed with stirring for 40 hours and is then cooled to ambient temperature and concentrated to dryness under reduced pressure. The residue is taken up in 200 ml of water, alkalinized with concentrated sodium hydroxide until the pH is 14, and then the mixture is extracted with 3×200 ml of dichloromethane. The organic phases are combined, washed with water, dried over magnesium sulfate, filtered, and then concentrated to dryness under reduced pressure. The residue is purified by chromatography on a 70 g cartridge of 15-40 μm silica, elution being carried out with pure cyclohexane and then with a 70/30 cyclohexane/dichloromethane mixture, at a flow rate of 50 ml/min. 0.56 g of (−)-4-fluoro-2-methylindoline is thus obtained in the form of a very pale yellow oil, the characteristics of which are the following:
Workup
- temperatureThe reaction mixture is refluxed
- concentrationconcentrated to dryness under reduced pressure
- extractionthe mixture is extracted with 3×200 ml of dichloromethane
- washwashed with water
- dry with materialdried over magnesium sulfate
- filtrationfiltered
- concentrationconcentrated to dryness under reduced pressure
- customThe residue is purified by chromatography on a 70 g cartridge of 15-40 μm silica, elution
Sources & evidence
- ORD record
- ord-9ed86b145ef645c4983c2fd7f12d9b8b
- Source dataset
- uspto-grants-2015_09
- Patent number
- US09133168B2
Reaction notes
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