Hydrochloric Acid → tert-butyl (2R,3S)-3-hydroxy-2-(hydroxymethyl)pyrrolidine-1-carboxylate

HRID 449826Notes

Reaction equation

HRID 449826 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH:10]([OH:13])[CH:9]1[C:14](O)=[O:15])=[O:7])([CH3:4])([CH3:3])[CH3:2].Cl>O1CCCC1.[OH-].[Na+]>[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][C@H:10]([OH:13])[C@H:9]1[CH2:14][OH:15])=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 2

HCID 313Hydrochloric AcidHCID 140370151-((Tert-butoxy)carbonyl)-3-hydroxypyrrolidine-2-carboxylic acid

Product 1

HCID 10910976tert-butyl (2R,3S)-3-hydroxy-2-(hydroxymethyl)pyrrolidine-1-carboxylateYield 80.3%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 14798Sodium HydroxideSolvent

Procedure

A solution of 3-hydroxy-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester (13.29 g, 57.47 mmol) in tetrahydrofuran (130 mL) is treated with borane-methyl sulfide complex (16.06 mL, 172.41 mmol) dropwise and stirred overnight at room temperature. The mixture is cooled to 5° C. in a water ice bath and treated with 3 N aqueous hydrogen chloride solution (5 mL) dropwise until evolution of gas has ceased. The resulting suspension is stirred further for 30 min and diluted with 5 N aqueous sodium hydroxide solution until a white solid is dissolved. This is extracted with ethyl acetate (3×100 mL). The organic layer is washed with water (2×100 mL) and brine, dried over sodium sulfate, filtered, and concentrated to dryness. The resulting oil is dried under vacuum to give 10.03 g (80%) of the title compound. LC-ES/MS m/z 457.2 [2M+Na]+, TR=1.59 min.

Workup

  1. temperatureThe mixture is cooled to 5° C. in a water ice bath
  2. stirringThe resulting suspension is stirred further for 30 min
  3. dissolutionis dissolved
  4. extractionThis is extracted with ethyl acetate (3×100 mL)
  5. washThe organic layer is washed with water (2×100 mL) and brine
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated to dryness
  9. customThe resulting oil is dried under vacuum

Sources & evidence

ORD record
ord-f4232fa70bd34095914341d1357deacb
Source dataset
uspto-grants-2013_07
Patent number
US08486943B2

Reaction notes

Loading…