Sulfuric Acid → (S)-2-Hydroxymethyl-azetidine-1-carboxylic acid benzyl ester

HRID 1858387Notes

Reaction equation

HRID 1858387 reaction equation
[NH:1]1[CH2:4][CH2:3][C@H:2]1[CH2:5][OH:6].S(=O)(=O)(O)O.C(=O)([O-])O.[Na+].[CH2:17]([O:24][C:25](Cl)=[O:26])[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1>>[CH2:17]([O:24][C:25]([N:1]1[CH2:4][CH2:3][C@H:2]1[CH2:5][OH:6])=[O:26])[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1

Participants

5

Reactant 4

HCID 1118Sulfuric AcidHCID 10387Benzyl chloroformateHCID 516892Sodium BicarbonateHCID 10855374(S)-Azetidin-2-ylmethanol

Product 1

HCID 10900173(S)-2-Hydroxymethyl-azetidine-1-carboxylic acid benzyl esterYield 49%

Procedure

Said solution of (S)-azetidine-2-methanol was adjusted to pH 10 by adding 10% sulfuric acid, sodium hydrogen carbonate (0.873 g, 10.5 mmol) was then added and benzyloxycarbonyl chloride (1.75 g, 10.5 mmol) was added at room temperature. Thereafter, stirring was continued for 14 hours. The reaction mixture was adjusted to pH 7 and extracted with ethyl acetate (50 mL×2), the extract was washed with water (50 mL×1), dried over magnesium sulfate and filtered, and the filtrate was concentrated. The concentrate was subjected to column chromatography (Wakogel C-200) using toluene/ethyl acetate as a mobile phase for separation/purification, to give (S)-N-benzyloxycarbonylazetidine-2-methanol as a pale yellow oil (0.495 g, yield 49%). As a byproduct, (S)-2-N-benzyloxycarbonyl-1,4-butanediol was obtained (0.26 g, yield 24%).

Workup

  1. additionwas then added
  2. extractionextracted with ethyl acetate (50 mL×2)
  3. washthe extract was washed with water (50 mL×1)
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationthe filtrate was concentrated
  7. customfor separation/purification

Sources & evidence

ORD record
ord-64e15868e6de4166ad9c966ff19d18f9
Source dataset
uspto-grants-2000_11
Patent number
US06150535

Reaction notes

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