4-Fluorophenol → HCID 57525235, compound

HRID 1470507Notes

Reaction equation

HRID 1470507 reaction equation
Cl[C:2]1[C:11]2[C:6](=[C:7]([CH3:12])[CH:8]=[CH:9][CH:10]=2)[C:5]([C:13]([N:15]2[CH2:20][CH2:19][O:18][CH2:17][CH2:16]2)=[O:14])=[CH:4][N:3]=1.[F:21][C:22]1[CH:27]=[CH:26][C:25]([OH:28])=[CH:24][CH:23]=1.C([O-])([O-])=O.[K+].[K+]>CN(C=O)C.[Cu]I>[F:21][C:22]1[CH:27]=[CH:26][C:25]([O:28][C:2]2[C:11]3[C:6](=[C:7]([CH3:12])[CH:8]=[CH:9][CH:10]=3)[C:5]([C:13]([N:15]3[CH2:20][CH2:19][O:18][CH2:17][CH2:16]3)=[O:14])=[CH:4][N:3]=2)=[CH:24][CH:23]=1

Participants

6

Reactant 3

HCID 97324-FluorophenolHCID 11430Potassium CarbonateHCID 86689597HCID 86689597, compound

Product 1

HCID 57525235HCID 57525235, compound

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
150 °C

Procedure

To a stirred solution of (1-chloro-5-methylisoquinolin-4-yl)(morpholino)methanone Intermediate-11a (1 equiv) in dry DMF (5 mL) was added, 4-fluorophenol (1.1 equiv), CuI (1.1 equiv) and K2CO3 (2 equiv) in a sealed tube. The reaction mixture was degassed for 20 min and then stirred at 150° C. for 2 h. It was allowed to reach RT and then diluted with EtOAc. The slurry was filtered through celite, and then washed with EtOAc. The solvent was then removed, and the residue was purified by column chromatography (15% EtOAc:Hexane) to afford the title compound; 1H NMR (400 MHz, CDCl3) δ 2.61 (s, 3H), 3.23-4.13 (m, 8H), 7.15-7.20 (m, 4H), 7.55-7.61 (m, 2H), 7.82 (s, 1H), 8.39-8.41 (m, 1H); MS m/z 367 (M+1).

Workup

  1. customThe reaction mixture was degassed for 20 min
  2. customto reach RT
  3. additiondiluted with EtOAc
  4. filtrationThe slurry was filtered through celite
  5. washwashed with EtOAc
  6. customThe solvent was then removed
  7. customthe residue was purified by column chromatography (15% EtOAc:Hexane)

Sources & evidence

ORD record
ord-3ec5706e278747a9b1d3b2a4186ae59c
Source dataset
uspto-grants-2015_04
Patent number
US09006442B2

Reaction notes

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