Methanesulfonic Acid → 5-Fluoro-2,2-dimethylindoline

HRID 2249936Notes

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]1

Participants

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-a8e320bd10a9476fbb40db1b10358767
Source dataset: uspto-grants-2008_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07314872B2

Reaction notes

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