Methanesulfonic Acid → 5-Fluoro-2,2-dimethylindoline
Reaction equation
C(OC(=O)[NH:7][C:8]1[CH:13]=[CH:12][C:11]([F:14])=[CH:10][C:9]=1[CH2:15][C:16]([CH3:18])=[CH2:17])(C)(C)C.C1(OC)C=CC=CC=1.FC(F)(F)C(O)=O.CS(O)(=O)=O>ClCCl>[CH3:17][C:16]1([CH3:18])[CH2:15][C:9]2[C:8](=[CH:13][CH:12]=[C:11]([F:14])[CH:10]=2)[NH:7]1Participants
Conditions
- Temperature
- 170 °C
Procedure
A sample of [4-Fluoro-2-(2-methyl-allyl)-phenyl]-carbamic acid tert-butyl ester (1.10 g, 4.14 mmol) was treated with anisole (5 mL), dichloromethane (5 mL) and trifluoroacetic acid (5 mL) and stirred for 4 hours. The solvent was removed and the reaction was transferred to a microwave reaction vial using methanesulfonic acid (3 mL). The reaction was heated to 170° C. for 10 minutes. The reaction was cooled to room temperature and quenched into excess stirring 1 M NaOH. The aqueous phase was extracted twice with ethyl acetate and the combined organics were dried over MgSO4 and filtered. The resulting oil was purified on silica gel using a gradient of 0-70% t-butyl ethyl ether and hexane to afford 450 mg (66% yield) of 2,2-dimethyl-5-fluoroindoline; 1H NMR (CDCl3, 400 MHz) δ 1.08 (s, 6H), 2.58 (s, 2H), 6.24 (dd, 1H, J1=4.4, J2=8.4), 6.43-6.48 (m, 1H), 6.53-6.56 (m, 1H); HPLC-MS calcd. for C10H12FN (M+H+) 166.1, found 166.4.
Workup
- customThe solvent was removed
- customthe reaction was transferred to a microwave reaction
- temperatureThe reaction was cooled to room temperature
- customquenched
- stirringinto excess stirring 1 M NaOH
- extractionThe aqueous phase was extracted twice with ethyl acetate
- dry with materialthe combined organics were dried over MgSO4
- filtrationfiltered
- customThe resulting oil was purified on silica gel using a gradient of 0-70% t-butyl ethyl ether and hexane
Sources & evidence
- ORD record
- ord-2f67e67fc24649c49722e2b7ba186b0a
- Source dataset
- uspto-grants-2008_06
- Patent number
- US07384970B2
Reaction notes
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