Anisole → HCID 66807266, compound

HRID 1843999Notes

Reaction equation

HRID 1843999 reaction equation
C1(OC)C=CC=CC=1.[F:9][C:10]1[CH:18]=[CH:17][C:16]2[N:15](CC3C=CC(OC)=CC=3)[C:14]3[CH:28]=[CH:29][N:30]([C:33]4[CH:34]=[N:35][CH:36]=[CH:37][C:38]=4[C:39]([F:42])([F:41])[F:40])[C:31](=[O:32])[C:13]=3[C:12]=2[CH:11]=1.C(OCC)(=O)C>C(O)(C(F)(F)F)=O.CCCCCC>[F:9][C:10]1[CH:18]=[CH:17][C:16]2[NH:15][C:14]3[CH:28]=[CH:29][N:30]([C:33]4[CH:34]=[N:35][CH:36]=[CH:37][C:38]=4[C:39]([F:41])([F:40])[F:42])[C:31](=[O:32])[C:13]=3[C:12]=2[CH:11]=1

Participants

6

Reactant 3

HCID 7519AnisoleHCID 8857Ethyl AcetateHCID 66804021HCID 66804021, compound

Product 1

HCID 66807266HCID 66807266, compoundYield 75%

Reagents, catalysts & solvents 2

HCID 6422Trifluoroacetic acidSolventHCID 8058HexaneSolvent

Conditions

Temperature
80 °C

Procedure

Anisole (0.25 mL) was added to a stirred solution of 8-fluoro-5-(4-methoxybenzyl)-2-(4-(trifluoromethyl)pyridin-3-yl)-2,5-dihydro-1H-pyrido[4,3-b]indol-1-one (I-64c: 95 mg, 0.203 mmol) in TFA (10 mL) under nitrogen atmosphere and the resulting reaction mass was refluxed at 80° C. overnight. The reaction was monitored by TLC (80% ethyl acetate in hexane). The reaction mass was cooled to room temperature, concentrated under reduced pressure, basified using NaHCO3 solution to pH 8 and extracted using ethyl acetate. The aqueous layer was extracted with ethyl acetate and the combined organic layers were concentrated under reduced pressure to afford the crude product. Purification by column chromatography on silica gel (2% methanol in DCM), followed by preparative HPLC afforded 9 mg of the product (75% yield).

Workup

  1. customthe resulting reaction mass
  2. temperatureThe reaction mass was cooled to room temperature
  3. concentrationconcentrated under reduced pressure
  4. extractionextracted
  5. extractionThe aqueous layer was extracted with ethyl acetate
  6. concentrationthe combined organic layers were concentrated under reduced pressure
  7. customto afford the crude product
  8. customPurification by column chromatography on silica gel (2% methanol in DCM)

Sources & evidence

ORD record
ord-572922f77de945e586aa59f2adf88cda
Source dataset
uspto-grants-2015_02
Patent number
US08946260B2

Reaction notes

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