Sodium hydride → HCID 58886089, compound

HRID 425897Notes

Reaction equation

HRID 425897 reaction equation
[F:1][C:2]1[C:3]([C:11]([F:14])([F:13])[F:12])=[C:4]([CH:8]([OH:10])[CH3:9])[CH:5]=[CH:6][CH:7]=1.[H-].[Na+].[CH3:17][O:18][C:19](=[O:44])[C:20]1[CH:25]=[CH:24][C:23]([C:26]2[CH:27]=[N:28][C:29]([NH2:43])=[C:30](OS(C3C=CC(C)=CC=3)(=O)=O)[CH:31]=2)=[CH:22][CH:21]=1>CN(C=O)C.CCOC(C)=O.O>[CH3:17][O:18][C:19](=[O:44])[C:20]1[CH:21]=[CH:22][C:23]([C:26]2[CH:27]=[N:28][C:29]([NH2:43])=[C:30]([O:10][CH:8]([C:4]3[CH:5]=[CH:6][CH:7]=[C:2]([F:1])[C:3]=3[C:11]([F:12])([F:13])[F:14])[CH3:9])[CH:31]=2)=[CH:24][CH:25]=1

Participants

7

Reactant 3

HCID 24758Sodium hydrideHCID 21111375HCID 21111375, compoundHCID 58886489HCID 58886489, compound

Product 1

HCID 58886089HCID 58886089, compoundYield 34%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

To a stirred solution of 1-(3-fluoro-2-trifluoromethyl-phenyl)-ethanol (2.0 g, 9.6 mmol) in anhydrous DMF (500 mL) at 0° C. under a N2 atmosphere was added NaH (0.38 g, 9.6 mmol). The reaction was allowed to stir for 0.5 hr. A solution of 4-[6-Amino-5-(toluene-4-sulfonyloxy)-pyridin-3-yl]-benzoic acid methyl ester (3.8 g, 9.6 mmol) in anhydrous DMF (30 mL) was added to the reaction mixture which was allowed to come to ambient temperature slowly and stirred for 21 hr at this temperature. The reaction was diluted with EtOAc (500 mL) and H2O (100 mL). The organic layer was separated off and the aqueous was further extracted with EtOAc (1×200 mL). The organic layers were combined and washed with brine (1×100 mL), dried with Na2SO4 and concentrated to dryness under vacuum. The crude mixture was purified by column chromatography (silica gel, 40:60 to 70:30 EtOAc:hexanes) and the fractions containing product were combined and concentrated in vacuo to yield 4-{6-amino-5-[1-(3-fluoro-2-trifluoromethyl-phenyl)-ethoxy]-pyridin-3-yl}-benzoic acid methyl ester (1.4 g, 3.2 mmol, 34%). 1H NMR (CDCl3, 300 MHz) δ 1.73 (d, 3H, J, 6.2 Hz), 3.91 (s, 3H), 4.87-4.64 (brs, 2H), 5.81 (q, 1H, J, 6.1; 6.3 Hz), 6.92 (d, 1H, J, 1.8 Hz), 7.38 (d, 2H, J, 8.5 Hz), 7.46-7.66 (m, 3H), 7.93 (d, 1H, J, 1.8 Hz), 8.02 (d, 2H, J, 8.5 Hz).

Workup

  1. customto come to ambient temperature
  2. stirringstirred for 21 hr at this temperature
  3. customThe organic layer was separated off
  4. extractionthe aqueous was further extracted with EtOAc (1×200 mL)
  5. washwashed with brine (1×100 mL)
  6. dry with materialdried with Na2SO4
  7. concentrationconcentrated to dryness under vacuum
  8. customThe crude mixture was purified by column chromatography (silica gel, 40:60 to 70:30 EtOAc:hexanes)
  9. additionthe fractions containing product
  10. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-c76c82e4e4514055854e577109efa76b
Source dataset
uspto-grants-2012_01
Patent number
US08106197B2

Reaction notes

Loading…