Benzyl chloroformate → Benzyl 3-hydroxyazetidine-1-carboxylate

HRID 1506841Notes

Reaction equation

HRID 1506841 reaction equation
[NH:1]1[CH2:4][CH:3]([OH:5])[CH2:2]1.C(=O)([O-])[O-].[K+].[K+].[C:12](Cl)(=[O:21])[O:13][CH2:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1>C1COCC1.O>[OH:5][CH:3]1[CH2:4][N:1]([C:12]([O:13][CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)=[O:21])[CH2:2]1

Participants

6

Reactant 3

HCID 10387Benzyl chloroformateHCID 11430Potassium CarbonateHCID 15142903-Hydroxyazetidine

Product 1

HCID 10081755Benzyl 3-hydroxyazetidine-1-carboxylateYield 69.8%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

A solution of azetidin-3-ol (14.7 g) dissolved in THF (170 mL) and water (85 mL) was treated with potassium carbonate (37.1 g) under nitrogen. The mixture was stirred at RT for 30 minutes before cooling to 0° C. and adding benzyl carbonochloridate (20.0 mL) dropwise over 30 minutes at 0° C. The resulting mixture was stirred at 20° C. for 60 hours. The reaction mixture was diluted with water (150 mL), and extracted with ethyl acetate (200 mL). The organic was dried over magnesium sulfate, filtered and evaporated to afford crude product as a colourless oil. The crude product was purified by flash silica chromatography, elution 50% ethyl acetate in isohexane to 100% ethyl acetate. Pure fractions were evaporated to dryness to afford the sub-title product (19.40 g, 69.8%) as a colorless oil.

Workup

  1. temperaturebefore cooling to 0° C.
  2. stirringThe resulting mixture was stirred at 20° C. for 60 hours
  3. extractionextracted with ethyl acetate (200 mL)
  4. dry with materialThe organic was dried over magnesium sulfate
  5. filtrationfiltered
  6. customevaporated
  7. customto afford crude product as a colourless oil
  8. customThe crude product was purified by flash silica chromatography, elution 50% ethyl acetate in isohexane to 100% ethyl acetate
  9. customPure fractions were evaporated to dryness

Sources & evidence

ORD record
ord-9d49e11a7df84b8caa27e777cf3c277e
Source dataset
uspto-grants-2015_12
Patent number
US09221782B2

Reaction notes

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