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

HRID 1858388Notes

Reaction equation

HRID 1858388 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 96%

Procedure

Said solution of (S)-azetidine-2-methanol was adjusted to pH 10 by adding 10% sulfuric acid, sodium hydrogen carbonate (0.44 g, 5.29 mmol) was then added, and benzyloxycarbonyl chloride (0.88 g, 5.16 mmol) was added thereto at room temperature, followed by 14 hours of stirring. The solution 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 (1/1) as a mobile phase for separation/purification, to give (S)-N-benzyloxycarbonylazetidine-2-methanol (0.499 g, yield 96%) as a pale yellow oil. (S)-2-N-benzyloxycarbonyl-1,4-butanediol was obtained as a byproduct (0.032 g, yield 6%).

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-830479ad1ad64e29b1fa3dfe11bd2f97
Source dataset
uspto-grants-2000_11
Patent number
US06150535

Reaction notes

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