Potassium bisulfate → tert-butyl (2S)-2-(hydroxymethyl)azetidine-1-carboxylate

HRID 1416592Notes

Reaction equation

HRID 1416592 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:11][CH2:10][C@H:9]1[C:12](O)=[O:13])=[O:7])([CH3:4])([CH3:3])[CH3:2].S([O-])(O)(=O)=O.[K+]>O1CCCC1>[C:1]([O:5][C:6]([N:8]1[CH2:11][CH2:10][C@H:9]1[CH2:12][OH:13])=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

4

Reactant 2

HCID 516920Potassium bisulfateHCID 2734495(2S)-1-((tert-butoxy)carbonyl)azetidine-2-carboxylic acid

Product 1

HCID 10511797tert-butyl (2S)-2-(hydroxymethyl)azetidine-1-carboxylateYield 96%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To an ice-cooled solution of the compound of step 7a (9.39 g, 46.72 mmol) in tetrahydrofuran (100 mL) was added borane/THF complex (1 M, 210 mL, 4.5 eq.) under nitrogen. The reaction was gradually warmed to room temperature and stirred for 48 hours, after which a 10% aqueous potassium hydrogen sulfate solution (60 mL) was added gradually, then the volatiles were evaporated in vacuo, . The remaining slurry was diluted with ethyl acetate (100 mL), and triturated two additional times. The organic phase was then washed with a saturated solution of sodium hydrogen carbonate (3×75 mL), dried (MgSO4), filtered and concentrated in vacuo, yielding a colorless oil (8.4 g, 96% yield). This material was carried forward without further purification. MS (DCI/NH3) m/e 188 (M+H)+. 1H NMR (CDCl3,300 MHz) δ: 4.49-4.40 (ddd, J=9.0 Hz, J=9.0 Hz, J=3.0 Hz, 1H), 3.95-3.68 (m, 4H), 2.23-2.12 (m, 1H), 1.99-1.87 (m, 111), 1.46 (s, 9H).

Workup

  1. additionwas added borane/THF complex (1 M, 210 mL, 4.5 eq.) under nitrogen
  2. customthe volatiles were evaporated in vacuo
  3. additionThe remaining slurry was diluted with ethyl acetate (100 mL)
  4. customtriturated two additional times
  5. washThe organic phase was then washed with a saturated solution of sodium hydrogen carbonate (3×75 mL)
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-260ca6014c9e49c1b1eecb468bf28390
Source dataset
uspto-grants-1999_06
Patent number
US05914328

Reaction notes

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