2-chloro-1-(oxolan-2-yl)ethanone

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: (RS)-2-Chloroacetyltetrahydrofuran (2.46g, 16.5mmol), (3R,4R)-4-mercapto-3-phenoxyacetamidoazetidin-2-one (4.157g, 16.5mmol) and potassium carbonate (2.227g 16.5mmol) in DMF (10ml) were stirred for 2h, diluted with ethyl acetate, washed twice with water and with brine, dried concentrated and flash chromatographed eluting with 40,30,20,10 and 0% hexane in ethyl acetate to give the title compound as a foam (3.547g, 59%); vmax (CH2Cl2) 3405, 1785, 1693, 1520, 1496 and 1240cm-1 ; δ(CDCl3, 250MHz) 1.9-2.3 (4H, m), 3.42 and 3.62, 3.46 and 3.56 (together 2H, 2 ABq, J15.8Hz, 15.4Hz), 3.85-4.0 (2H, m), 4.4-4.5 (1H, m), 4.58 (2H, s), 5.01, 5.04 (together 1H, 2d, J4.7Hz), 5.59 (1H, dd, J 8.8, 4.5Hz) 6.62, 6.68 (together 1H, 2s), 6.9-7.4 (5H, m) and 7.45, 7.47 (together 1H, 2d, J8.8Hz). [Mass spectrum: M+ (364)]. washed twice with water and with brine dried concentrated flash chromatographed eluting with 40,30,20,10 and 0% hexane in ethyl acetate

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Oxalyl chloride (5.2ml, 60mmol) and DMF (1 drop) were added to (RS)-2-tetrahydrofuroic acid (W. E. Kaufmann and R. Adams, J.Amer.Chem.Soc., 1923, 45, 3029) (4.64g, 40mmol) in dichloromethane (25ml). The mixture was stirred 1h, evaporated in vacuo, dichloromethane added and reevaporated to give 2-tetrahydrofuroyl chloride, vmax (CH2Cl2) 1795cm-1. 2-Tetrahydrofuroyl chloride in ether (25ml) and dichloromethane (10ml) was added dropwise to an ice bath cooled solution of diazomethane (ca 80mmol) in ether (150ml). The reaction mixture was stirred 0.25h then a stream of hydrogen chloride gas passed into the solution for ca 2 minutes then stirred a further 0.25h, washed with saturated brine, dried, concentrated and flash chromatographed on silica gel eluting with 5,7.5 and 10% ethyl acetate in hexane to provide the title compound (2.46g, 41%); (Found: M+, 148.0279. C6H ClO2 requires M, 148.0291); vmax (CH2Cl2) 1739, 1395, 1071 and 936cm-1 ; δH (CDCl3, 250MHz) 1.8-2.4 (4H, m) and 3.9-4.6 (5H, m). washed with saturated brine dried concentrated flash chromatographed on silica gel eluting with 5,7.5 and 10% ethyl acetate in hexane

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: (RS)-2-Chloroacetyltetrahydrofuran (2.46 g, 16.5 mmol), (3R,4R)-4-mercapto-3-phenoxyacetamidoazetidin-2-one (4.157 g, 16.5 mmol) and potassium carbonate (2.227 g 16.5 mmol) in DMF (10 ml) were stirred for 2 h, diluted with ethyl acetate, washed twice with water and with brine, dried concentrated and flash chromatographed eluting with 40, 30, 20, 10 and 0% hexane in ethyl acetate to give the title compound as a foam (3.547 g, 59%); νmax (CH2Cl2) 3405, 1785, 1693, 1520, 1496 and 1240 cm-1 ; δ(CDCl3, 250 MHz) 1.9-2.3 (4 H, m), 3.42 and 3.62, 3.46 and 3.56 (together 2 H, 2 ABq, J15.8 Hz, 15.4 Hz), 3.85-4.0 (2 H, m), 4.4-4.5 (1 H, m), 4.58 (2 H, s), 5.01, 5.04 (together 1 H, 2 d, J4.7 Hz), 5.59 (1 H, dd, J 8.8, 4.5 Hz) 6.62, 6.68 (together 1 H, 2 s), 6.9-7.4 (5 H, m) and 7.45, 7.47 (together 1 H, 2 d, J8.8 Hz). [Mass spectrum: M+ (364)]. washed twice with water and with brine dried concentrated flash chromatographed eluting with 40, 30, 20, 10 and 0% hexane in ethyl acetate

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Oxalyl chloride (5.2 ml, 60 mmol) and DMF (1 drop) were added to (RS)-2-tetrahydrofuroic acid (W. E. Kaufmann and R. Adams, J.Amer.Chem.Soc., 1923, 45, 3029) (4.64 g, 40 mmol) in dichloromethane (25 ml). The mixture was stirred 1 h, evaporated in vacuo, dichloromethane added and reevaporated to give 2-tetrahydrofuroyl chloride, νmax (CH2Cl2) 1795 cm-1. 2-Tetrahydrofuroyl chloride in ether (25 ml) and dichloromethane (10 ml) was added dropwise to an ice bath cooled solution of diazomethane (ca 80 mmol) in ether (150 ml). The reaction mixture was stirred 0.25 h then a stream of hydrogen chloride gas passed into the solution for ca 2 minutes then stirred a further 0.25 h, washed with saturated brine, dried, concentrated and flash chromatographed on silica gel eluting with 5,7.5 and 10% ethyl acetate in hexane to provide the title compound (2.46 g, 41%); (Found: M+, 148.0279. C6H9ClO2 requires M, 148.0291); νmax (CH2Cl2) 1739, 1395, 1071 and 936 cm-1 ; δH (CDCl3, 250 MHz) 1.8-2.4 (4 H, m) and 3.9-4.6 (5 H, m). then stirred a further 0.25 h washed with saturated brine dried concentrated flash chromatographed on silica gel eluting with 5,7.5 and 10% ethyl acetate in hexane

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Oxalyl chloride (5.2 ml, 60 mmol) and DMF (1 drop) were added to (RS)-2-tetrahydrofuroic acid (W. E. Kaufmann and R. Adams, J.Amer.Chem.Soc., 1923, 45, 3029) (4.64 g, 40 mmol) in dichloromethane (25 ml). The mixture was stirred 1 h, evaporated in vacuo, dichloromethane added and reevaporated to give 2-tetrahydrofuroyl chloride, νmax (CH2Cl2) 1795 cm-1. 2-Tetrahydrofuroyl chloride in ether (25 ml) and dichloromethane (10 ml) was added dropwise to an ice bath cooled solution of diazomethane (ca 80 mmol) in ether (150 ml). The reaction mixture was stirred 0.25 h then a stream of hydrogen chloride gas passed into the solution for ca 2 minutes then stirred a further 0.25 h, washed with saturated brine, dried, concentrated and flash chromatographed on silica gel eluting with 5,7.5 and 10% ethyl acetate in hexane to provide the title compound (2.46 g, 41%); (Found: M+, 148.0279. C6H9ClO2 requires M, 148.0291); νmax (CH2Cl2) 1739, 1395, 1071 and 936 cm-1 ; δH (CDCl3, 250 MHz) 1.8-2.4 (4 H, m) and 3.9-4.6 (5 H, m). then stirred a further 0.25 h washed with saturated brine dried concentrated flash chromatographed on silica gel eluting with 5,7.5 and 10% ethyl acetate in hexane

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: (RS)-2-Chloroacetyltetrahydrofuran (2.46g, 16.5mmol), (3R,4R)-4-mercapto-3-phenoxyacetamidoazetidin-2-one (4.157g, 16.5mmol) and potassium carbonate (2.227g 16.5mmol) in DMF (10ml) were stirred for 2h, diluted with ethyl acetate, washed twice with water and with brine, dried concentrated and flash chromatographed eluting with 40,30,20,10 and 0% hexane in ethyl acetate to give the title compound as a foam (3.547g, 59%); vmax (CH2Cl2) 3405, 1785, 1693, 1520, 1496 and 1240cm-1 ; δ(CDCl3, 250MHz) 1.9-2.3 (4H, m), 3.42 and 3.62, 3.46 and 3.56 (together 2H, 2 ABq, J15.8Hz, 15.4Hz), 3.85-4.0 (2H, m), 4.4-4.5 (1H, m), 4.58 (2H, s), 5.01, 5.04 (together 1H, 2d, J4.7Hz), 5.59 (1H, dd, J 8.8, 4.5Hz) 6.62, 6.68 (together 1H, 2s), 6.9-7.4 (5H, m) and 7.45, 7.47 (together 1H, 2d, J8.8Hz). [Mass spectrum: M+ (364)]. washed twice with water and with brine dried concentrated flash chromatographed eluting with 40,30,20,10 and 0% hexane in ethyl acetate

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: (RS)-2-Chloroacetyltetrahydrofuran (2.46g, 16.5mmol), (3R,4R)-4-mercapto-3-phenoxyacetamidoazetidin-2-one (4.157g, 16.5mmol) and potassium carbonate (2.227g 16.5mmol) in DMF (10ml) were stirred for 2h, diluted with ethyl acetate, washed twice with water and with brine, dried concentrated and flash chromatographed eluting with 40,30,20,10 and 0% hexane in ethyl acetate to give the title compound as a foam (3.547g, 59%); vmax (CH2Cl2) 3405, 1785, 1693, 1520, 1496 and 1240cm-1 ; δ(CDCl3, 250MHz) 1.9-2.3 (4H, m), 3.42 and 3.62, 3.46 and 3.56 (together 2H, 2 ABq, J15.8Hz, 15.4Hz), 3.85-4.0 (2H, m), 4.4-4.5 (1H, m), 4.58 (2H, s), 5.01, 5.04 (together 1H, 2d, J4.7Hz), 5.59 (1H, dd, J 8.8, 4.5Hz) 6.62, 6.68 (together 1H, 2s), 6.9-7.4 (5H, m) and 7.45, 7.47 (together 1H, 2d, J8.8Hz). [Mass spectrum: M+ (364)]. washed twice with water and with brine dried concentrated flash chromatographed eluting with 40,30,20,10 and 0% hexane in ethyl acetate

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Oxalyl chloride (5.2ml, 60mmol) and DMF (1 drop) were added to (RS)-2-tetrahydrofuroic acid (W. E. Kaufmann and R. Adams, J.Amer.Chem.Soc., 1923, 45, 3029) (4.64g, 40mmol) in dichloromethane (25ml). The mixture was stirred 1h, evaporated in vacuo, dichloromethane added and reevaporated to give 2-tetrahydrofuroyl chloride, vmax (CH2Cl2) 1795cm-1. 2-Tetrahydrofuroyl chloride in ether (25ml) and dichloromethane (10ml) was added dropwise to an ice bath cooled solution of diazomethane (ca 80mmol) in ether (150ml). The reaction mixture was stirred 0.25h then a stream of hydrogen chloride gas passed into the solution for ca 2 minutes then stirred a further 0.25h, washed with saturated brine, dried, concentrated and flash chromatographed on silica gel eluting with 5,7.5 and 10% ethyl acetate in hexane to provide the title compound (2.46g, 41%); (Found: M+, 148.0279. C6H ClO2 requires M, 148.0291); vmax (CH2Cl2) 1739, 1395, 1071 and 936cm-1 ; δH (CDCl3, 250MHz) 1.8-2.4 (4H, m) and 3.9-4.6 (5H, m). washed with saturated brine dried concentrated flash chromatographed on silica gel eluting with 5,7.5 and 10% ethyl acetate in hexane

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Oxalyl chloride (5.2ml, 60mmol) and DMF (1 drop) were added to (RS)-2-tetrahydrofuroic acid (W. E. Kaufmann and R. Adams, J.Amer.Chem.Soc., 1923, 45, 3029) (4.64g, 40mmol) in dichloromethane (25ml). The mixture was stirred 1h, evaporated in vacuo, dichloromethane added and reevaporated to give 2-tetrahydrofuroyl chloride, vmax (CH2Cl2) 1795cm-1. 2-Tetrahydrofuroyl chloride in ether (25ml) and dichloromethane (10ml) was added dropwise to an ice bath cooled solution of diazomethane (ca 80mmol) in ether (150ml). The reaction mixture was stirred 0.25h then a stream of hydrogen chloride gas passed into the solution for ca 2 minutes then stirred a further 0.25h, washed with saturated brine, dried, concentrated and flash chromatographed on silica gel eluting with 5,7.5 and 10% ethyl acetate in hexane to provide the title compound (2.46g, 41%); (Found: M+, 148.0279. C6H ClO2 requires M, 148.0291); vmax (CH2Cl2) 1739, 1395, 1071 and 936cm-1 ; δH (CDCl3, 250MHz) 1.8-2.4 (4H, m) and 3.9-4.6 (5H, m). washed with saturated brine dried concentrated flash chromatographed on silica gel eluting with 5,7.5 and 10% ethyl acetate in hexane

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: (RS)-2-Chloroacetyltetrahydrofuran (2.46 g, 16.5 mmol), (3R,4R)-4-mercapto-3-phenoxyacetamidoazetidin-2-one (4.157 g, 16.5 mmol) and potassium carbonate (2.227 g, 16.5 mmol) in DMF (10 ml) were stirred for 2 h, diluted with ethyl acetate, washed twice with water and with brine, dried concentrated and flash chromatographed eluting with 40,30,20,10 and 0% hexane in ethyl acetate to give the title compound as a foam (3.547 g, 59%); νmax (CH2Cl2) 3405, 1785, 1693, 1520, 1496 and 1240 cm-1 ; δ(CDCl3, 250 MHz) 1.9-2.3 (4H, m), 3.42 and 3.62, 3.46 and 3.56 (together 2H, 2 ABq, J15.8 Hz, 15.4 Hz), 3.85-4.0 (2H, m), 4.4-4.5 (1H, m), 4.58 (2H, s), 5.01, 5.04 (together 1H, 2d, J4.7 Hz), 5.59 (1H, dd, J 8.8, 4.5 Hz) 6.62, 6.68 (together 1H, 2s), 6.9-7.4 (5H, m) and 7.45, 7.47 (together 1H, 2d, J8.8 Hz). [Mass spectrum: M+ (364)]. washed twice with water and with brine dried concentrated flash chromatographed eluting with 40,30,20,10 and 0% hexane in ethyl acetate

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Oxalyl chloride (5.2 ml, 60 mmol) and DMF (1 drop) were added to (RS)-2-tetrahydrofuroic acid (W. E. Kaufmann and R. Adams, J.Amer.Chem.Soc., 1923, 45, 3029) (4.64 g, 40 mmol) in dichloromethane (25 ml). The mixture was stirred 1 h, evaporated in vacuo, dichloromethane added and reevaporated to give 2-tetrahydrofuroyl chloride, νmax (CH2Cl2) 1795 cm-1. 2-Tetrahydrofuroyl chloride in ether (25 ml) and dichloromethane (10 ml) was added dropwise to an ice bath cooled solution of diazomethane (ca 80 mmol) in ether (150 ml). The reaction mixture was stirred 0.25 h then a stream of hydrogen chloride gas passed into the solution for ca 2 minutes then stirred a further 0.25 h, washed with saturated brine, dried, concentrated and flash chromatographed on silica gel eluting with 5, 7.5 and 10% ethyl acetate in hexane to provide the title compound (2.46 g, 41%); (Found: M+, 148.0279. C6H9ClO2 requires M, 148.0291); νmax (CH2Cl2) 1739, 1395, 1071 and 936 cm-1 ; δH (CDCl3, 250 MHz) 1.8-2.4 (4H, m) and 3.9-4.6 (5H, m). then stirred a further 0.25 h washed with saturated brine dried concentrated flash chromatographed on silica gel eluting with 5, 7.5 and 10% ethyl acetate in hexane

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: (RS)-2-Chloroacetyltetrahydrofuran (2.46 g, 16.5 mmol), (3R,4R)-4-mercapto-3-phenoxyacetamidoazetidin-2-one (4.157 g, 16.5 mmol) and potassium carbonate (2.227 g 16.5 mmol) in DMF (10 ml) were stirred for 2 h, diluted with ethyl acetate, washed twice with water and with brine, dried concentrated and flash chromatographed eluting with 40, 30, 20, 10 and 0% hexane in ethyl acetate to give the title compound as a foam (3.547 g, 59%); νmax (CH2Cl2) 3405, 1785, 1693, 1520, 1496 and 1240 cm-1 ; δ(CDCl3, 250 MHz) 1.9-2.3 (4 H, m), 3.42 and 3.62, 3.46 and 3.56 (together 2 H, 2 ABq, J15.8 Hz, 15.4 Hz), 3.85-4.0 (2 H, m), 4.4-4.5 (1 H, m), 4.58 (2 H, s), 5.01, 5.04 (together 1 H, 2 d, J4.7 Hz), 5.59 (1 H, dd, J 8.8, 4.5 Hz) 6.62, 6.68 (together 1 H, 2 s), 6.9-7.4 (5 H, m) and 7.45, 7.47 (together 1 H, 2 d, J8.8 Hz). [Mass spectrum: M+ (364)]. washed twice with water and with brine dried concentrated flash chromatographed eluting with 40, 30, 20, 10 and 0% hexane in ethyl acetate