BENZYL 3-HYDROXYAZETIDINE-1-CARBOXYLATE

BENZYL 3-HYDROXYAZETIDINE-1-CARBOXYLATE Property

Boiling point:

356.7±42.0 °C(Predicted)

Density 

1.317

Flash point:

169.5℃

storage temp. 

2-8°C

form 

solid

pka

14.14±0.20(Predicted)

color 

White

InChI

InChI=1S/C11H13NO3/c13-10-6-12(7-10)11(14)15-8-9-4-2-1-3-5-9/h1-5,10,13H,6-8H2

InChIKey

XJWSNDGCJMGHSR-UHFFFAOYSA-N

SMILES

N1(C(OCC2=CC=CC=C2)=O)CC(O)C1

Safety

HS Code 

29339900

Hazard and Precautionary Statements (GHS)

Symbol(GHS)

Signal word

Warning

Hazard statements

H315Causes skin irritation

H319Causes serious eye irritation

H335May cause respiratory irritation

Precautionary statements

P280Wear protective gloves/protective clothing/eye protection/face protection.

P302+P352IF ON SKIN: wash with plenty of soap and water.

BENZYL 3-HYDROXYAZETIDINE-1-CARBOXYLATE Chemical Properties,Usage,Production

Synthesis

General procedure for the synthesis of 1-Benzyloxycarbonyl-3-hydroxyazetidine from 3-hydroxyazetidine hydrochloride and benzyl chloroformate: K2CO3 (63.1 g, 0.46 mol) was added to a mixed solution of water (150 mL) and THF (300 mL) containing azetidin-3-ol hydrochloride (25 g, 0.23 mol). The reaction mixture was stirred at 20-25 °C for 30 min. Subsequently, benzyl chloroformate (40.9 g, 0.24 mol) was added slowly and dropwise over 30 min. The reaction mixture was first stirred at 0-5°C and then continued to stir overnight at 20-25°C. Upon completion of the reaction, THF was removed under reduced pressure using a rotary evaporator at 30 °C. The remaining mixture was extracted with ethyl acetate (2 × 150 mL). The organic layers were combined, washed with water (1 × 50 mL), dried with Na2SO4 and concentrated. The residue was purified by silica gel fast column chromatography using ethyl acetate-heptane (1:1 and 4:1) sequentially as eluent to afford the target product, 1-benzyloxycarbonyl-3-hydroxyazetidine (47.3 g, 100%), as a clear oil. The product was characterized by 1H NMR (300 MHz, CDCl3), 13C NMR (75 MHz, CDCl3), IR and ES-HRMS, and the data were consistent with the expected structure.

References

[1] Organic Process Research and Development, 2009, vol. 13, # 1, p. 54 - 59
[2] Patent: WO2010/36329, 2010, A2. Location in patent: Page/Page column 16-17; 21
[3] Chemical Communications, 2012, vol. 48, # 45, p. 5578 - 5580
[4] Patent: WO2016/128529, 2016, A1. Location in patent: Paragraph 0800; 0801; 0802
[5] Patent: WO2014/32, 2014, A1. Location in patent: Page/Page column 33