Potassium Carbonate → 8-Fluoro-5-methoxy-2-methylquinoline

HRID 1051572Notes

Reaction equation

HRID 1051572 reaction equation
[F:1][C:2]1[CH:8]=[CH:7][C:6]([O:9][CH3:10])=[CH:5][C:3]=1[NH2:4].Cl.Cl[C:13]1[CH:14]=CC(OC)=[C:17]2[C:22]=1N=C(C)C=C2.COC1C=CC=C2C=1CC[C@H](C)N2.C(=O)([O-])[O-].[K+].[K+]>ClCCl>[F:1][C:2]1[CH:8]=[CH:7][C:6]([O:9][CH3:10])=[C:5]2[C:3]=1[N:4]=[C:22]([CH3:17])[CH:13]=[CH:14]2

Participants

6

Reactant 4

HCID 11430Potassium CarbonateHCID 135590752-Fluoro-5-methoxyanilineHCID 754807178-Chloro-5-methoxy-2-methylquinoline hydrochlorideHCID 118075405(S)-5-methoxy-2-methyl-1,2,3,4-tetrahydroquinoline

Product 1

HCID 1180758218-Fluoro-5-methoxy-2-methylquinolineYield 62%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

8-Fluoro-5-methoxy-2-methylquinoline was synthesized from 2-fluoro-5-methoxyaniline (30.0 g, 213 mmol) according to the procedures described above for 8-chloro-5-methoxy-2-methylquinoline hydrochloride (Intermediate 1, Step 1) with the following change: The hydrochloride salt was dissolved in dichloromethane (400 mL) and the pH of the resulting solution was adjusted to 8-9 with saturated aqueous potassium carbonate solution. The resulting mixture was extracted with dichloromethane, and the combined organic layers were dried over anhydrous sodium sulfate, filtered, and concentrated under vacuum. The residue was purified via column chromatography on silica gel (eluting with 20% ethyl acetate-petroleum ether) to afford 8-fluoro-5-methoxy-2-methylquinoline (25.2 g, 62%) as a yellow solid. MS (ESI, pos. ion) m/z 192 [M+H]+.

Workup

  1. extractionThe resulting mixture was extracted with dichloromethane
  2. dry with materialthe combined organic layers were dried over anhydrous sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated under vacuum
  5. customThe residue was purified via column chromatography on silica gel (eluting with 20% ethyl acetate-petroleum ether)

Sources & evidence

ORD record
ord-56d47b0c1f1147ebb9c5b0a1c41bdf6a
Source dataset
uspto-grants-2016_07
Patent number
US09388161B2

Reaction notes

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