Cesium carbonate → 6-(4-Fluoro-2-methylphenoxy)-1,2,3,4-tetrahydronaphthalen-1-one

HRID 63629

Reaction equation

HRID 63629 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[C:8](=[O:12])[CH2:7][CH2:6][CH2:5]2.[F:13][C:14]1[CH:19]=[CH:18][C:17]([OH:20])=[C:16]([CH3:21])[CH:15]=1.N1C=CC=CC=1CC(C)=O.C([O-])([O-])=O.[Cs+].[Cs+]>CS(C)=O.O>[F:13][C:14]1[CH:19]=[CH:18][C:17]([O:20][C:2]2[CH:3]=[C:4]3[C:9](=[CH:10][CH:11]=2)[C:8](=[O:12])[CH2:7][CH2:6][CH2:5]3)=[C:16]([CH3:21])[CH:15]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 959101-(Pyridin-2-yl)propan-2-oneHCID 1362954-Fluoro-2-methylphenolHCID 101050696-Bromo-1-tetralone

Product 1

HCID 1185981606-(4-Fluoro-2-methylphenoxy)-1,2,3,4-tetrahydronaphthalen-1-oneYield 95.6%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

To a suspension of 6-bromo-1,2,3,4-tetrahydronaphthalen-1-one (2.0 g, 8.9 mmol), 4-fluoro-2-methylphenol (1.7 g, 13.3 mmol), 1-pyridin-2-ylacetone (240 mg, 1.8 mmol) and Cs2CO3 (5.8 g, 17.8 mmol) in DMSO (40 mL) was added CuBr (127 mg, 0.9 mmol) at rt under N2. The reaction was stirred at 100° C. overnight. The reaction was cooled, diluted with water (50 mL), and extracted with EtOAc (3×50 mL). Organics were washed with water (3×50 mL) and brine (50 mL), dried (Na2SO4), and concentrated. Purification by silica gel chromatography (PE:EtOAc=30:1) gave 2.3 g (95%) of the title compound as a colorless oil. [M+H] Calc'd for C17H15FO2, 271. Found, 271.

Workup

  1. temperatureThe reaction was cooled
  2. extractionextracted with EtOAc (3×50 mL)
  3. washOrganics were washed with water (3×50 mL) and brine (50 mL)
  4. dry with materialdried (Na2SO4)
  5. concentrationconcentrated
  6. customPurification by silica gel chromatography (PE:EtOAc=30:1)

Sources & evidence

ORD record
ord-1d69527dfb824fd28985ca2c6f39fa80
Source dataset
uspto-grants-2016_09
Patent number
US09447046B2

Linked notes

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