Lithium triethylborohydride → (2R,3R)-3-(tert-Butyldimethylsilanyloxy)-2-hydroxymethylpyrrolidine-1-carboxylic acid tert-butyl ester

HRID 501590Notes

Reaction equation

HRID 501590 reaction equation
C[O:2][C:3]([C@@H:5]1[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@H:5]1[CH2:3][OH:2])=[O:19])([CH3:24])([CH3:23])[CH3:22]

Participants

4

Reactant 2

HCID 23712863Lithium triethylborohydrideHCID 68455583(2S,3R)-3-(tert-Butyldimethylsilanyloxy)pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl ester

Product 1

HCID 11012982(2R,3R)-3-(tert-Butyldimethylsilanyloxy)-2-hydroxymethylpyrrolidine-1-carboxylic acid tert-butyl esterYield 90.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To (2S,3R)-3-(tert-Butyl-dimethyl-silanyloxy)-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl ester (51A) (8.05 g, 22.39 mmol) in THF (90 mL) at −78° C. was added a 1 M solution of Super-Hydride® in THF (112 mL, 112 mmol) in five portions over 15 min The cold bath was removed and the reaction was allowed to warm to rt. After 3 h, 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, NaHCO3 and brine, dried (MgSO4), filtered and concentrated. The residue was diluted with CH2Cl2, stirred with silica gel overnight, then concentrated and purified via flash chromatography eluting with 30% EtOAc/hexane to obtain the title compound (6.70 g) as a clear oil.

Workup

  1. customwas removed
  2. additionthe reaction was poured into a 1-L Erlenmeyer flask
  3. customwas carefully quenched with ice
  4. additiondiluted with EtOAc
  5. customThe layers were separated
  6. washthe organic layer washed with 1 M H3PO4, NaHCO3 and brine
  7. dry with materialdried (MgSO4)
  8. filtrationfiltered
  9. concentrationconcentrated
  10. additionThe residue was diluted with CH2Cl2
  11. stirringstirred with silica gel overnight
  12. concentrationconcentrated
  13. custompurified via flash chromatography
  14. washeluting with 30% EtOAc/hexane

Sources & evidence

ORD record
ord-411964c0e07241ca9e3ed9c23c4c2fe7
Source dataset
uspto-grants-2010_08
Patent number
US07772267B2

Reaction notes

Loading…