Boron trifluoride etherate → HCID 67492993, compound

HRID 1922168Notes

Reaction equation

HRID 1922168 reaction equation
C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[C:11]([O:15][C:16]([N:18]1[CH2:22][CH2:21][CH2:20][C:19]1=[O:23])=[O:17])([CH3:14])([CH3:13])[CH3:12].[CH3:24][CH:25]([CH3:29])[CH2:26][CH:27]=[O:28].B(F)(F)F.CCOCC>C1COCC1>[C:11]([O:15][C:16]([N:18]1[CH2:22][CH2:21][CH:20]([CH:27]([OH:28])[CH2:26][CH:25]([CH3:29])[CH3:24])[C:19]1=[O:23])=[O:17])([CH3:14])([CH3:12])[CH3:13]

Participants

6

Reactant 4

HCID 8000Boron trifluoride etherateHCID 115523-MethylbutanalHCID 3790001-Pyrrolidinecarboxylic acid, 2-oxo-, 1,1-dimethylethyl esterHCID 2733832Lithium Hexamethyldisilazide

Product 1

HCID 67492993HCID 67492993, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Add lithium bis(trimethyl silyl)-amide (1.0 M in THF, 148 mL, 148 mmol) to a solution of 2-oxo-pyrrolidine-1-carboxylic acid tert-butyl ester (25.0 g, 134 mmol) in THF (450 mL) at −78° C. and stir under nitrogen for 2 hours. Add 3-methyl-butyraldehyde (17.5 mL, 162 mmol) followed by boron trifluoride diethyl etherate (20.5 mL, 162 mmol) and continue to stir at −78° C. for 2 hours. Warm the mixture to room temperature, quench with saturated aqueous ammonium chloride (250 mL) and extract with EtOAc (3×). Dry the combined organics (Na2SO4), filter and concentrate under reduced pressure. Divide the crude product into two equal portions and purify each portion by silica gel chromatography, eluting with 0-40% EtOAc in hexanes to provide 3-(1-hydroxy-3-methyl-butyl)-2-oxo-pyrrolidine-1-carboxylic acid tert-butyl ester, diastereomer 1 (12.5 g, 34%) (D1) as the first eluting isomer, MS (m/z)=216.0 (M−56), and 3-(1-hydroxy-3-methyl-butyl)-2-oxo-pyrrolidine-1-carboxylic acid tert-butyl ester, diastereomer 2 (3.87 g, 11%) (D2) as the second eluting isomer. MS (m/z)=216.0 (M−56)

Workup

  1. stirringto stir at −78° C. for 2 hours
  2. customquench with saturated aqueous ammonium chloride (250 mL)
  3. extractionextract with EtOAc (3×)
  4. dry with materialDry the combined organics (Na2SO4)
  5. filtrationfilter
  6. concentrationconcentrate under reduced pressure
  7. custompurify each portion by silica gel chromatography
  8. washeluting with 0-40% EtOAc in hexanes

Sources & evidence

ORD record
ord-4035d3f448914dcd92f259d600daa9af
Source dataset
uspto-grants-2012_05
Patent number
US08173821B2

Reaction notes

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