Sodium hydride → HCID 86637443, compound

HRID 1851733Notes

Reaction equation

HRID 1851733 reaction equation
[H-].[Na+].[CH2:3]([C@H:6]1[CH2:10][NH:9][C:8](=[O:11])[CH2:7]1)[CH2:4][CH3:5].[CH3:12][O:13][C:14](=[O:20])[C:15](C)(Br)[CH2:16][CH3:17]>O1CCCC1.O>[CH3:12][O:13][C:14](=[O:20])[CH:15]([N:9]1[CH2:10][C@H:6]([CH2:3][CH2:4][CH3:5])[CH2:7][C:8]1=[O:11])[CH2:16][CH3:17]

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 16059240HCID 16059240, compoundHCID 22902551Methyl 2-bromo-2-methylbutanoate

Product 1

HCID 86637443HCID 86637443, compoundYield 86%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
0 °C

Procedure

A slurry of 60% sodium hydride suspension in mineral oil (0.94 g, 23.4 mmol) in tetrahydrofuran (30 mL) is cooled at 0° C. under a nitrogen atmosphere. A solution of substantially optically pure (R)-4-propyl-pyrrolidin-2-one (IIIa) (2 g, 15.7 mmol) in tetrahydrofuran (2 mL) is added over a 15 minutes period. The reaction mixture is stirred 10 min at 0° C. then a solution of methyl-2-bromo-butyric acid methyl ester (V) (3.69 g, 20.4 mmol) in tetrahydrofuran (2 mL) was added over a 20 minutes period. The reaction mixture is stirred at 0° C. until maximum conversion of starting material and the reaction mixture is then allowed to warm to room temperature and diluted with water (20 mL). Tetrahydrofuran is removed by evaporation and the residue is extracted with isopropyl acetate (20 ml+10 mL). The combined organic layers are dried on anhydrous magnesium sulfate and evaporated to afford 3 g (13.2 mmol, 86%) of a mixture of epimers of compound (VIa), as a mixture respectively of epimer (VIaa) and epimer (VIab).

Workup

  1. stirringThe reaction mixture is stirred at 0° C. until maximum conversion of starting material
  2. temperatureto warm to room temperature
  3. customTetrahydrofuran is removed by evaporation
  4. extractionthe residue is extracted with isopropyl acetate (20 ml+10 mL)
  5. dry with materialThe combined organic layers are dried on anhydrous magnesium sulfate
  6. customevaporated

Sources & evidence

ORD record
ord-f1d963020e684945a2ff3a07057ee560
Source dataset
uspto-grants-2015_02
Patent number
US08957226B2

Reaction notes

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