Ethyl Acetate → [6-Fluoro-3-methyl-4-(4-nitro-phenyl)-naphthalen-2-yl]-acetic acid methyl ester

HRID 1468350Notes

Reaction equation

HRID 1468350 reaction equation
[CH3:1][O:2][C:3](=[O:25])[CH2:4][C:5]1[C:14]([CH3:15])=[C:13](OS(C(F)(F)F)(=O)=O)[C:12]2[C:7](=[CH:8][CH:9]=[C:10]([F:24])[CH:11]=2)[CH:6]=1.[N+:26]([C:29]1[CH:34]=[CH:33][C:32](B(O)O)=[CH:31][CH:30]=1)([O-:28])=[O:27].C(=O)([O-])[O-].[Cs+].[Cs+].C(OCC)(=O)C>C(COC)OC.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[CH3:1][O:2][C:3](=[O:25])[CH2:4][C:5]1[C:14]([CH3:15])=[C:13]([C:32]2[CH:33]=[CH:34][C:29]([N+:26]([O-:28])=[O:27])=[CH:30][CH:31]=2)[C:12]2[C:7](=[CH:8][CH:9]=[C:10]([F:24])[CH:11]=2)[CH:6]=1

Participants

7

Reactant 4

HCID 8857Ethyl AcetateHCID 10796Cesium carbonateHCID 27735524-Nitrophenylboronic acidHCID 59326772(6-Fluoro-3-methyl-4-trifluoromethanesulfonyloxy-naphthalen-2-yl)-acetic acid methyl ester

Product 1

HCID 86694943[6-Fluoro-3-methyl-4-(4-nitro-phenyl)-naphthalen-2-yl]-acetic acid methyl esterYield 42.6%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 80711,2-DimethoxyethaneSolvent

Procedure

To a mixture of (6-fluoro-3-methyl-4-trifluoromethanesulfonyloxy-naphthalen-2-yl)-acetic acid methyl ester (500 mg, 1.31 mmol), 4-nitrophenylboronic acid (658.5 mg, 3.94 mmol) and cesium carbonate (865.6 mg, 2.63 mmol) in dimethoxyethane (5 mL) was added [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (144.3 mg, 0.2 mmol) at room temperature under nitrogen. The resulting mixture was reacted using a microwave reactor (Personal Chemistry) at 120° C. for 30 minutes. Ethyl acetate (50 mL) was added and the organic layer was washed with water (30 ml) and brine solution (20 mL). The organic layers were dried over anhydrous magnesium sulfate, filtered, and concentrated in vacuo to give the crude product which was purified using an ISCO (90 g) column, eluting with 5-15% ethyl acetate in hexanes, to give [6-fluoro-3-methyl-4-(4-nitro-phenyl)-naphthalen-2-yl]-acetic acid methyl ester (197 mg, 42%) as a light yellow solid. 1H NMR (300 MHz, CDCl3), δ ppm 8.40 (d, J=8.6 Hz, 2 H), 7.82 (dd, J=8.9, 5.7 Hz, 1 H), 7.77 (s, 1 H), 7.46 (d, J=8.6 Hz, 2 H), 7.21 (td, J=8.9, 2.4 Hz, 1 H), 6.76 (dd, J=11.2, 2.4 Hz, 1 H), 3.87 (s, 2 H), 3.74 (s, 3 H), 2.14 (s, 3 H). HRMS calcd. for C20H15FNO4 [(M−H)−] 352.0990, obsd. 352.0990.

Workup

  1. customThe resulting mixture was reacted
  2. customat 120° C.
  3. customfor 30 minutes
  4. washthe organic layer was washed with water (30 ml) and brine solution (20 mL)
  5. dry with materialThe organic layers were dried over anhydrous magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customto give the crude product which
  9. customwas purified
  10. washeluting with 5-15% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-1691332de4724f8b815238cc4d983301
Source dataset
uspto-grants-2015_04
Patent number
US09000044B2

Reaction notes

Loading…