Dimethylformamide → HCID 86695025, compound

HRID 1468443Notes

Reaction equation

HRID 1468443 reaction equation
[CH3:1][S:2]([C:5]1[CH:10]=[CH:9][C:8](B(O)O)=[CH:7][CH:6]=1)(=[O:4])=[O:3].[CH3:14][O:15][C:16](=[O:38])[CH2:17][C:18]1[C:27]([CH3:28])=[C:26](OS(C(F)(F)F)(=O)=O)[C:25]2[C:20](=[CH:21][CH:22]=[C:23]([F:37])[CH:24]=2)[CH:19]=1.C(=O)([O-])[O-].[Cs+].[Cs+].CN(C=O)C>[Cl-].[Na+].O.C(OCC)(=O)C.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]>[CH3:14][O:15][C:16](=[O:38])[CH2:17][C:18]1[C:27]([CH3:28])=[C:26]([C:8]2[CH:9]=[CH:10][C:5]([S:2]([CH3:1])(=[O:4])=[O:3])=[CH:6][CH:7]=2)[C:25]2[C:20](=[CH:21][CH:22]=[C:23]([F:37])[CH:24]=2)[CH:19]=1

Participants

8

Reactant 4

HCID 6228DimethylformamideHCID 10796Cesium carbonateHCID 27343644-(Methanesulfonyl)phenylboronic acidHCID 59326772(6-Fluoro-3-methyl-4-trifluoromethanesulfonyloxy-naphthalen-2-yl)-acetic acid methyl ester

Product 1

HCID 86695025HCID 86695025, compoundYield 85%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 8857Ethyl AcetateSolvent2×HCID 57417360Sodium chloride; waterSolvent

Procedure

To a mixture of 4-(methanesulfonyl)benzeneboronic acid (146 mg, 0.734 mmol), (6-fluoro-3-methyl-4-trifluoromethanesulfonyloxy-naphthalen-2-yl)-acetic acid methyl ester (93 mg, 0.244 mmol), 1,1′-bis(diphenylphosphino)ferrocenedichloropalladium (II) (36 mg, 0.048 mmol), and cesium carbonate (239 mg, 0.734 mmol) was added anhydrous DMF (5 mL) at room temperature. The resulting light brown suspension was heated to reflux for 15 hours. The reaction mixture was cooled to room temperature and diluted with brine and ethyl acetate. The two layers were separated and the aqueous layer was extracted with ethyl acetate and the combined extracts were washed with brine. The organic layer was dried over anhydrous MgSO4, filtered, and concentrated to give the crude residue. Flash chromatography (80 g ISCO column, 0-45% ethyl acetate in hexanes) gave 80 mg (85%) of [6-fluoro-4-(4-methansulfonyl-phenyl)-3-methyl-naphthalen-2-yl]-acetic acid methyl ester. 1H NMR (300 MHz, CDCl3) δ ppm 8.11 (d, J=8.2 Hz, 2 H), 7.82 (dd, J=8.7, 5.9 Hz, 1 H), 7.77 (s, 1 H), 7.49 (d, J=8.2 Hz, 2 H), 7.21 (td, J=8.7, 2.3 Hz, 1 H), 6.77 (dd, J=11.2, 2.3 Hz, 1 H), 3.87 (s, 2 H), 3.74 (s, 3 H), 3.20 (s, 3 H), 2.13 (s, 3 H). HRMS cald. for C21H20FO4S [(M+H)+] 387.1061, obsd. 387.1059.

Workup

  1. temperatureThe resulting light brown suspension was heated
  2. temperatureto reflux for 15 hours
  3. customThe two layers were separated
  4. extractionthe aqueous layer was extracted with ethyl acetate
  5. washthe combined extracts were washed with brine
  6. dry with materialThe organic layer was dried over anhydrous MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customto give the crude residue

Sources & evidence

ORD record
ord-8f269fb54f754366a90f4e5eb17870e3
Source dataset
uspto-grants-2015_04
Patent number
US09000044B2

Reaction notes

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