Sodium Carbonate → 2-(4-Fluoro-phenyl)-6-methoxy-1-methoxymethoxy-3-methyl-naphthalene

HRID 1993008Notes

Reaction equation

HRID 1993008 reaction equation
Br[C:2]1[C:11]([CH3:12])=[CH:10][C:9]2[C:4](=[CH:5][CH:6]=[C:7]([O:13][CH3:14])[CH:8]=2)[C:3]=1[O:15][CH2:16][O:17][CH3:18].[F:19][C:20]1[CH:21]=[C:22](B(O)O)[CH:23]=[CH:24][CH:25]=1.C(=O)([O-])[O-].[Na+].[Na+]>C1(P([Pd-4](P(C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(P(C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)P(C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.COCCOC>[F:19][C:20]1[CH:21]=[CH:22][C:23]([C:2]2[C:11]([CH3:12])=[CH:10][C:9]3[C:4](=[CH:5][CH:6]=[C:7]([O:13][CH3:14])[CH:8]=3)[C:3]=2[O:15][CH2:16][O:17][CH3:18])=[CH:24][CH:25]=1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 27339863-Fluorophenylboronic acidHCID 685362562-Bromo-6-methoxy-1-(methoxymethoxy)-3-methylnaphthalene

Product 1

HCID 685374682-(4-Fluoro-phenyl)-6-methoxy-1-methoxymethoxy-3-methyl-naphthaleneYield 84.2%

Reagents, catalysts & solvents 2

HCID 178420553HCID 178420553, compoundCatalystHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
160 °C

Procedure

2-Bromo-6-methoxy-1-(methoxymethoxy)-3-methylnaphthalene (14) (2.00 g, 6.44 mmol), 3-fluorobenzeneboronic acid (1.80 g, 12.88 mmol), tetrakis(triphenylphosphino)palladium (0) (0.74 g, 0.64 mmol), 2 M sodium carbonate (60 mL) and ethylene glycol dimethyl ether (60 mL) were combined and heated in a sealed tube at 160° C. for 75 min. The reaction was cooled to room temperature and filtered through a celite pad with 100 mL each diethyl ether and water. The organic layer was washed with brine (100 mL), dried (Na2SO4) and concentrated to an orange viscous oil. The crude product was purified by column chromatography with 10% EtOAc/hexane to afford 1.77 g (84%) of the title compound, 283 as a yellow oil. 1H NMR (400 MHz, DMSO-d6): δ 2.14 (s, 3H), 3.02 (s, 3H), 3.86 (s, 3H), 4.71 (s, 3H), 7.12-7.23 (m, 4H), 7.25 (d, J=2.5 Hz, 1H), 7.46-7.52 (m, 1H), 7.53 (s, 1H), 7.93 (d, J=9.2 Hz, 1H).

Workup

  1. temperatureThe reaction was cooled to room temperature
  2. filtrationfiltered through a celite pad with 100 mL each diethyl ether and water
  3. washThe organic layer was washed with brine (100 mL)
  4. dry with materialdried (Na2SO4)
  5. concentrationconcentrated to an orange viscous oil
  6. customThe crude product was purified by column chromatography with 10% EtOAc/hexane

Sources & evidence

ORD record
ord-8cb530d40a464f5baaa9a51492e9b366
Source dataset
uspto-grants-2010_01
Patent number
US07649093B2

Reaction notes

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