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

HRID 751120Notes

Reaction equation

HRID 751120 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 triethylborohydrideHCID 68459339(2S,3R)-3-(tert-Butyldimethylsilanyloxy)-2-methylpyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester-2-methyl ester

Product 1

HCID 68457239(2R,3R)-3-(tert-Butyldimethylsilanyloxy)-2-hydroxymethyl-2-methylpyrrolidine-1-carboxylic acid tert-butyl esterYield 53.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of (2S,3R)-3-(tert-Butyldimethylsilanyloxy)-2-methylpyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester-2-methyl ester (58A) (1.08 g, 2.90 mmol) in THF (12 mL) at −78° C. was added a 1 M solution of Super-Hydride® in THF (14.50 mL, 14.50 mmol) in three portions over 15 min. After 10 min, the cold bath was removed and the reaction was allowed to warm to rt and was stirred for 18 h. The reaction was cooled again to −78° C. and more Super-Hydride® (7 mL) was added. After stirring an additional 24 h, the reaction was poured into a 1-L Erlenmeyer flask containing ice water and was then diluted with EtOAc. The layers were separated and the organic layer washed with 1 M H3PO4 (2×), NaHCO3 and brine, dried (MgSO4), filtered and concentrated under reduced pressure. The residue was diluted with CH2Cl2, stirred with silica gel for 10 min, then concentrated under reduced pressure and purified via flash chromatography, eluting with 20% EtOAc/hexane to obtain the title compound (0.54 g) as a clear oil. MS m/z 346 [M+H]+.

Workup

  1. customthe cold bath was removed
  2. temperatureThe reaction was cooled again to −78° C.
  3. additionmore Super-Hydride® (7 mL) was added
  4. stirringAfter stirring an additional 24 h
  5. additionthe reaction was poured into a 1-L Erlenmeyer flask
  6. additioncontaining ice water
  7. additionwas then diluted with EtOAc
  8. customThe layers were separated
  9. washthe organic layer washed with 1 M H3PO4 (2×), NaHCO3 and brine
  10. dry with materialdried (MgSO4)
  11. filtrationfiltered
  12. concentrationconcentrated under reduced pressure
  13. additionThe residue was diluted with CH2Cl2
  14. stirringstirred with silica gel for 10 min
  15. concentrationconcentrated under reduced pressure
  16. custompurified via flash chromatography
  17. washeluting with 20% EtOAc/hexane

Sources & evidence

ORD record
ord-13969c64056c48b69275d86c775ff632
Source dataset
uspto-grants-2008_07
Patent number
US07405234B2

Reaction notes

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