Sodium hydride → {5-[5-Bromo-6-(2-chloro-4-fluoro-phenoxy)-pyridine-3-sulfonylamino]-5,6,7,8-tetrahydro-naphthalen-1-yloxy}-acetic acid tert-butyl ester

HRID 1696880Notes

Reaction equation

HRID 1696880 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[OH:9].[H-].[Na+].[C:12]([O:16][C:17](=[O:42])[CH2:18][O:19][C:20]1[C:29]2[CH2:28][CH2:27][CH2:26][CH:25]([NH:30][S:31]([C:34]3[CH:35]=[N:36][C:37](Cl)=[C:38]([Br:40])[CH:39]=3)(=[O:33])=[O:32])[C:24]=2[CH:23]=[CH:22][CH:21]=1)([CH3:15])([CH3:14])[CH3:13]>CN(C)C=O>[C:12]([O:16][C:17](=[O:42])[CH2:18][O:19][C:20]1[C:29]2[CH2:28][CH2:27][CH2:26][CH:25]([NH:30][S:31]([C:34]3[CH:35]=[N:36][C:37]([O:9][C:3]4[CH:4]=[CH:5][C:6]([F:8])=[CH:7][C:2]=4[Cl:1])=[C:38]([Br:40])[CH:39]=3)(=[O:32])=[O:33])[C:24]=2[CH:23]=[CH:22][CH:21]=1)([CH3:15])([CH3:13])[CH3:14]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 748142-Chloro-4-fluorophenolHCID 59192603[5-(5-Bromo-6-chloro-pyridine-3-sulfonylamino)-5,6,7,8-tetrahydro-naphthalen-1-yloxy]-acetic acid tert-butyl ester

Product 1

HCID 59192570{5-[5-Bromo-6-(2-chloro-4-fluoro-phenoxy)-pyridine-3-sulfonylamino]-5,6,7,8-tetrahydro-naphthalen-1-yloxy}-acetic acid tert-butyl ester

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

To a stirred solution of 2-chloro-4-fluoro-phenol (292 mg, 2.0 mmol) in N,N-dimethylformamide (5 mL) was added sodium hydride (28.8 mg, 1.2 mmol) portionwise at 0° C. under nitrogen and stirred at the same temperature for 15 minutes. To the above mixture was added [5-(5-bromo-6-chloro-pyridine-3-sulfonylamino)-5,6,7,8-tetrahydro-naphthalen-1-yloxy]-acetic acid tert-butyl ester (212 mg, 0.4 mmol) portionwise at 0° C. Then the reaction mixture was heated at 100° C. overnight. After being cooled to room temperature, the reaction was quenched with water (2 mL), and diluted with ethyl acetate (50 mL). The resulting solution was washed subsequently with water (10 mL), 1N sodium hydroxide solution (10 mL), and brine (10 mL). The organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo to give {5-[5-bromo-6-(2-chloro-4-fluoro-phenoxy)-pyridine-3-sulfonylamino]-5,6,7,8-tetrahydro-naphthalen-1-yloxy}-acetic acid tert-butyl ester, which was used in the next step without further purification. MS cald. for C27H27BrClFN2O6S 640, obsd. 641 [(M+H)+].

Workup

  1. temperatureAfter being cooled to room temperature
  2. customthe reaction was quenched with water (2 mL)
  3. additiondiluted with ethyl acetate (50 mL)
  4. washThe resulting solution was washed subsequently with water (10 mL), 1N sodium hydroxide solution (10 mL), and brine (10 mL)
  5. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-3050b90a599a452aae03f4faa559484c
Source dataset
uspto-grants-2012_04
Patent number
US08163781B2

Reaction notes

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