Azetidine-1,2-dicarboxylic acid 1-tert-butyl ester Chemical Properties

Boiling point:

321.0±35.0 °C(Predicted)

Density 

1.246±0.06 g/cm3(Predicted)

storage temp. 

2-8°C

pka

4.01±0.20(Predicted)

form 

solid

color 

Pale yellow

InChI

InChI=1S/C9H15NO4/c1-9(2,3)14-8(13)10-5-4-6(10)7(11)12/h6H,4-5H2,1-3H3,(H,11,12)

InChIKey

JWJVSDZKYYXDDN-UHFFFAOYSA-N

SMILES

N1(C(OC(C)(C)C)=O)CCC1C(O)=O

Safety Information

Hazard Codes 

Xi,N

Risk Statements 

36/37/38-50

Safety Statements 

26-36-61-24/25

RIDADR 

UN3077

WGK Germany 

3

HS Code 

29339900

MSDS

• Language:English Provider:SigmaAldrich

Azetidine-1,2-dicarboxylic acid 1-tert-butyl ester Usage And Synthesis

Description

Azetidine-1,2-dicarboxylic acid 1-tert-butyl ester (ADCBT) is a pyrrolidinyl nicotinic acetylcholine receptor agonist. ADCBT has been shown to have affinity values for neuronal nicotinic acetylcholine receptors that are significantly higher than those of nicotine. It has been shown to be regioselective in the sense that it binds preferentially to the alpha4beta2 subtype of the nicotinic acetylcholine receptor, which is present in both peripheral and central neurons. It also has a high affinity for the acetylcholine binding site at the neuromuscular junction. ADCBT has been shown to have analgesic effects in animal studies.

Chemical Properties

White powder

Uses

Azetidine-1,2-dicarboxylic acid 1-tert-butyl ester, is an useful intermediate in the synthesis of pharmaceutical compounds including inhibitors and receptor Antagonists. It can be used in the synthesis of polypeptides.

Preparation

Sodium hydroxide (2.08 g, 51.92 mmol) was added to a solution of azetidine-2-carboxylic acid (5.00 g, 49.50 mmol), di-tert-butyl dicarbonate (13.50 g, 61.80 mmol) in ethanol (120.0 mL) at 0 °C. After stirring the reaction mixture for 8 hours, the pH of the mixture was adjusted to 2 with 1.0 N HCl and extracted with ethyl acetate (2 × 200 mL). The combined organic layers were washed with brine, separated, and dried over anhydrous sodium sulfate. Then the compound was concentrated under reduced pressure to afford Azetidine-1,2-dicarboxylic acid 1-tert-butyl ester.

Synthesis

The general procedure for the synthesis of N-Boc-azetidine-2-carboxylic acid from (S)-2-azetidinecarboxylic acid (10 g, 98.9 mmol), di-tert-butyl dicarbonate (28.06 g, 128.6 mmol), N-methylmorpholine (11.5 g, 113.7 mmol), and 1,4-dioxane (160 mL) was as follows: the above mixture was 0 °C for 4 hours, followed by continued stirring at room temperature for 18 hours. After completion of the reaction, the volatile solvent was removed by evaporation and the residue was dissolved in water and washed with dichloromethane (DCM). The aqueous layer was acidified to pH 1.0 with concentrated hydrochloric acid at 0 °C and subsequently extracted with DCM. The organic layer was dried with anhydrous sodium sulfate (Na2SO4) to give the final N-tert-butoxycarbonylazetidine-2-carboxylic acid (12.61 g, 63.1% yield) as an oily product. Its nuclear magnetic resonance hydrogen spectrum (NMR, CDCl3) data were as follows: δ 1.42 (s, 9H), 2.40 (m, 1H), 2.59 (m, 1H), 3.90 (m, 2H), 4.80 (t, 1H).

References

[1] Patent: WO2006/100461, 2006, A1. Location in patent: Page/Page column 79
[2] Patent: US5409946, 1995, A

Azetidine-1,2-dicarboxylic acid 1-tert-butyl ester(159749-28-7)Related Product Information

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