1-Azetidinecarboxylic acid, 3-methylene-, 1,1-dimethylethyl ester Chemical Properties

Boiling point:

214.8±29.0 °C(Predicted)

Density 

1.02±0.1 g/cm3(Predicted)

storage temp. 

2-8°C

form 

clear liquid

pka

-1.56±0.20(Predicted)

color 

Colorless to Almost colorless

InChI

InChI=1S/C9H15NO2/c1-7-5-10(6-7)8(11)12-9(2,3)4/h1,5-6H2,2-4H3

InChIKey

MECAHFSQQZQZOI-UHFFFAOYSA-N

SMILES

N1(C(OC(C)(C)C)=O)CC(=C)C1

Safety Information

HS Code 

2933998090

1-Azetidinecarboxylic acid, 3-methylene-, 1,1-dimethylethyl ester Usage And Synthesis

Uses

tert-Butyl 3-Methyleneazetidine-1-carboxylate is a useful reagent used in the preparation of functionalized difluorocyclopropanes as building blocks for drug discoveries.

Uses

tert-Butyl 3-Methyleneazetidine-1-carboxylate is a useful reagent used in the preparation of functionalized difluorocyclopropanes as building blocks for drug discoveries.

Synthesis

The general procedure for the synthesis of 1-Boc-3-methylene azetidine from 1-Boc-3-azetidinone and methyltriphenylphosphonium bromide was as follows: first, a mixture of potassium ethanol/tert-butanol (15.5 g, 137 mmol) and methyltriphenylphosphonium bromide (49 g, 137 mmol) in ethyl ether (300 mL) was stirred for 1 hour at room temperature. Subsequently, 1-Boc-3-azetidinone (10 g, 58 mmol, dissolved in 100 mL of ether) was added to the reaction system. The reaction mixture was continued to be stirred at 35°C for 2 hours, after which it was cooled to room temperature. The reaction mixture was filtered through a diatomaceous earth pad and the filter cake was washed with ether. The combined filtrates were extracted by partitioning with water, washed twice each sequentially with water and brine, and the organic phase was dried over anhydrous sodium sulfate, filtered, and concentrated in vacuum to give an orange-colored oil. The crude product was purified by column chromatography using a hexane solution of 10% ethyl acetate as eluent. The target fraction was collected and concentrated in vacuum to give 1-Boc-3-methylene azetidine (9.80 g, 58 mmol, 100% yield) as a colorless oil. The structure of the product was confirmed by 1H NMR (400 MHz, DMSO) and GC-MS: 1H NMR (400 MHz, DMSO): δ 5.05-4.85 (m, 2H), 4.95-4.63 (m, 4H), 1.45 (s, 9H); GC-MS (C9H15NO2): m/z 169.

References

[1] Patent: WO2007/44515, 2007, A1. Location in patent: Page/Page column 175
[2] Patent: WO2008/76415, 2008, A1. Location in patent: Page/Page column 339-340
[3] Patent: WO2008/124085, 2008, A2. Location in patent: Page/Page column 190
[4] ACS Medicinal Chemistry Letters, 2012, vol. 3, # 5, p. 416 - 421
[5] Patent: WO2012/4400, 2012, A1. Location in patent: Page/Page column 47-48

1-Azetidinecarboxylic acid, 3-methylene-, 1,1-dimethylethyl ester(934664-41-2)Related Product Information

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