Sodium hydride → (S)-2-[5-Bromo-2-oxo-3-(4-trifluoromethylbenzoylamino)-2H-pyridin-1-yl]-3-phenylpropionic acid methyl ester

HRID 7806

Reaction equation

HRID 7806 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([NH:9][C:10](=[O:21])[C:11]2[CH:16]=[CH:15][C:14]([C:17]([F:20])([F:19])[F:18])=[CH:13][CH:12]=2)[C:5]([OH:8])=[N:6][CH:7]=1.[H-].[Na+].[CH3:24][O:25][C:26](=[O:40])[C@H:27](OS(C)(=O)=O)[CH2:28][C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1>O1CCCC1.C(OCC)(=O)C>[CH3:24][O:25][C:26](=[O:40])[C@@H:27]([N:6]1[CH:7]=[C:2]([Br:1])[CH:3]=[C:4]([NH:9][C:10](=[O:21])[C:11]2[CH:12]=[CH:13][C:14]([C:17]([F:18])([F:19])[F:20])=[CH:15][CH:16]=2)[C:5]1=[O:8])[CH2:28][C:29]1[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=1

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 12096286(R)-2-Methanesulfonyloxy-3-phenylpropionic acid methyl esterHCID 178418902HCID 178418902, compound

Product 1

HCID 69587645(S)-2-[5-Bromo-2-oxo-3-(4-trifluoromethylbenzoylamino)-2H-pyridin-1-yl]-3-phenylpropionic acid methyl esterYield 70.1%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of N-(5-bromo-2-hydroxypyridin-3-yl)-4-trifluoromethyl-benzamide from Step D (760 mg, 2.1 mmol) in tetrahydrofuran (10 mL) was added 95% sodium hydride (80 mg, 3.15 mmol) at room temperature. After the reaction mixture was stirred at room temperature for 30 min, (R)-2-methanesulfonyloxy-3-phenylpropionic acid methyl ester from Step B (820 mg, 3.15 mmol) was added and the reaction was stirred and heated at 50° C. for 20 h. The reaction mixture was cooled to room temperature and diluted with ethyl acetate (100 mL) and washed with saturated ammonium chloride solution and brine. The organic layer was separated, dried with sodium sulfate, filtered and concentrated in vacuo. Purification by medium pressure liquid chromatography on silica gel (1:6 ethyl acetate/hexanes) gave 770 mg (70%) of the title compound as a semisolid.

Workup

  1. stirringthe reaction was stirred
  2. temperatureheated at 50° C. for 20 h
  3. temperatureThe reaction mixture was cooled to room temperature
  4. washwashed with saturated ammonium chloride solution and brine
  5. customThe organic layer was separated
  6. dry with materialdried with sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customPurification by medium pressure liquid chromatography on silica gel (1:6 ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-5d20f741e39649beb44e6c36ba4af93d
Source dataset
uspto-grants-2006_08
Patent number
US07087622B2

Linked notes

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