Chemical Properties
Colorless to yellow liquid
Uses
Benzyloxyacetyl chloride is a reagent used to construct substituted 2-azetidinones for further elaboration into annulated β-lactams. It is a commonly employed reagent for asymmetric synthesis of β-lactams. It is also used in preparation of (S)-3-(methylamino)-3-((R)-pyrrolidin-3-yl)propanenitrile, key intermediate in the preparation of fluoroquinolone antibiotic for respiratory tract infections, non-racemic helicene and β-lactams.
Uses
Commonly employed reagent for asymmetric synthesis of β-lactams.1,2
Synthesis
Example 1 (a) Synthesis of benzyloxyacetyl chloride: to a solution of dichloromethane (50 mL) containing benzyloxyacetic acid (10.0 g, 60.0 mmol, 8.6 mL) was sequentially added oxalyl chloride (9.1 g, 72.0 mmol, 6.0 mL) and N,N-dimethylformamide (DMF, 30.0 mg, 0.4 mmol, 32.0 μL). The reaction mixture was stirred for 3 h at room temperature. Rapid gas release was observed at the beginning of the reaction, which gradually stopped as the reaction progressed. Upon completion of the reaction, the dichloromethane solution was concentrated under reduced pressure to give a colloidal product. Subsequently, additional oxalyl chloride (4.5 g, 35.7 mmol, 3.0 mL), dichloromethane (50 mL), and a drop of DMF were added to the gelatinous product, and the reaction mixture was again stirred for 2 h, during which a rapid gas release was observed. Finally, the reaction mixture was concentrated under reduced pressure to afford benzyloxyacetyl chloride (1) 11.0 g (in quantitative yield) as a gel. The structure of the product was confirmed by 13C NMR (75 MHz, CDCl3) with chemical shifts of δ 73.6, 74.8, 128.1, 128.4, 128.6, 130.0 and 171.9.
References
[1] Patent: US2013/177501, 2013, A1. Location in patent: Paragraph 0152
[2] Patent: WO2015/7834, 2015, A1. Location in patent: Page/Page column 17
[3] Patent: WO2015/40087, 2015, A1. Location in patent: Page/Page column 13; 14
[4] Patent: US9168317, 2015, B2. Location in patent: Page/Page column 20
[5] Patent: US9314541, 2016, B2. Location in patent: Page/Page column 21
