Lithium triethylborohydride → (2S,3S)-3-(tert-Butyldimethylsilanyloxy)-2-hydroxymethyl-2-methylpyrrolidine-1-carboxylic Acid Tert-Butyl Ester

HRID 1864691Notes

Reaction equation

HRID 1864691 reaction equation
C[O:2][C:3]([C@@:5]1([CH3:25])[C@@H:9]([O:10][Si:11]([C:14]([CH3:17])([CH3:16])[CH3:15])([CH3:13])[CH3:12])[CH2:8][CH2:7][N:6]1[C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])=O.[Li+].[B-](CC)(CC)CC>C1COCC1>[C:21]([O:20][C:18]([N:6]1[CH2:7][CH2:8][C@H:9]([O:10][Si:11]([C:14]([CH3:17])([CH3:16])[CH3:15])([CH3:13])[CH3:12])[C@@:5]1([CH2:3][OH:2])[CH3:25])=[O:19])([CH3:24])([CH3:23])[CH3:22]

Participants

4

Reactant 2

HCID 23712863Lithium triethylborohydride2×HCID 57974635(2R,3S)-3-tert-butyldimethylsilanyloxy-2-methylpyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl Ester

Product 1

HCID 57974660(2S,3S)-3-(tert-Butyldimethylsilanyloxy)-2-hydroxymethyl-2-methylpyrrolidine-1-carboxylic Acid Tert-Butyl EsterYield 24.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
-78 °C

Procedure

To compound 3B (0.519 g, 1.39 mmol) in THF (10 mL) at −78° C. was added a 1 M solution of Super-Hydride® in THF (9.73 mL, 9.73 mmol). The cold bath was removed and the reaction was stirred for 2.5 days. The reaction was cooled to −78° C., additional 1 M Super-Hydride® in THF (4.00 mL, 4.00 mmol) was added, and reaction was stirred overnight at rt. The reaction was poured into a 1-L Erlenmeyer flask and was carefully quenched with ice while stirring and then diluted with EtOAc. The layers were separated and the organic layer washed with 1 M H3PO4, saturated aqueous NaHCO3 and brine, dried (MgSO4), filtered and concentrated. The residue was purified via flash chromatography eluting with 20-50% EtOAc/hexane to obtain compound 3C (117 mg) as a clear oil.

Workup

  1. customThe cold bath was removed
  2. customreaction
  3. stirringwas stirred overnight at rt
  4. customwas carefully quenched with ice
  5. stirringwhile stirring
  6. additiondiluted with EtOAc
  7. customThe layers were separated
  8. washthe organic layer washed with 1 M H3PO4, saturated aqueous NaHCO3 and brine
  9. dry with materialdried (MgSO4)
  10. filtrationfiltered
  11. concentrationconcentrated
  12. customThe residue was purified via flash chromatography
  13. washeluting with 20-50% EtOAc/hexane

Sources & evidence

ORD record
ord-2888daab477d46f59e33ee4ba8838d5d
Source dataset
uspto-grants-2009_12
Patent number
US07625923B2

Reaction notes

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