Sodium hydride → HCID 86637444, compound

HRID 1851734Notes

Reaction equation

HRID 1851734 reaction equation
[H-].[Na+].[F:3][C:4]([F:12])=[CH:5][C@H:6]1[CH2:10][NH:9][C:8](=[O:11])[CH2:7]1.[CH3:13][O:14][C:15](=[O:21])[C:16](C)(Br)[CH2:17][CH3:18]>O1CCCC1.O>[CH3:13][O:14][C:15](=[O:21])[CH:16]([N:9]1[CH2:10][C@H:6]([CH:5]=[C:4]([F:12])[F:3])[CH2:7][C:8]1=[O:11])[CH2:17][CH3:18]

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 16059241HCID 16059241, compoundHCID 22902551Methyl 2-bromo-2-methylbutanoate

Product 1

HCID 86637444HCID 86637444, compoundYield 89%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
0 °C

Procedure

A slurry of 60% sodium hydride suspension in mineral oil (0.80 g, 20.4 mmol) in tetrahydrofuran (28 mL) is cooled at 0° C. under a nitrogen atmosphere. A solution of substantially optically pure (S)-4-(2,2-difluoro-vinyl)-pyrrolidin-2-one (IIIb) (2 g, 13.6 mmol) in tetrahydrofuran (8 mL) is added over a 30 minutes period. The reaction mixture is stirred 10 minutes at 0° C. then a solution of 2-bromo-butyric acid methyl ester (V) (3.20 g, 17.6 mmol) in tetrahydrofuran (2 mL) is added over a 15 minutes period. The reaction mixture is stirred at 0° C. for 4.5 h then the reaction mixture is allowed to warm to room temperature and diluted with water (15 mL). Tetrahydrofuran is removed by evaporation and the residue is extracted with isopropyl acetate (2×10 mL). The combined organic layers are dried over anhydrous magnesium sulfate and evaporated to afford 3 g (12.1 mmol, 89%) of compound (VIb), as a mixture respectively of epimer (VIba) and epimer (VIbb).

Workup

  1. stirringThe reaction mixture is stirred at 0° C. for 4.5 h
  2. temperatureto warm to room temperature
  3. customTetrahydrofuran is removed by evaporation
  4. extractionthe residue is extracted with isopropyl acetate (2×10 mL)
  5. dry with materialThe combined organic layers are dried over anhydrous magnesium sulfate
  6. customevaporated

Sources & evidence

ORD record
ord-aec4695f1dba418d9080ebb9949d8284
Source dataset
uspto-grants-2015_02
Patent number
US08957226B2

Reaction notes

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