4-(chloromethyl)-4-methyl-1,3-oxazolidin-2-one

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 4-(chloromethyl)-4-methyloxazolidin-2-one (1.49 g, 9.96 mmol) in DMF (100 ml) was added sodium bromide (11.02 g, 107 mmol), and the suspension heated to 80° C. for 6 h. The suspension was concentrated in vacuo and the residue purified by flash chromatography (30% to 60% ethyl acetate in hexanes) to give the title compound as a white solid (1.33 g, 6.86 mmol, 66%). 1H NMR (CDCl3, 400 MHz) δ 1.54 (s, 3H), 3.47 (s, 2H), 4.14 (d, J=9.2 Hz, 1H), 4.35 (d, J=8.8 Hz, 1H), 6.24 (br s, 1H). LRMS (ESI/APCI): 194 [M+H]+. The suspension was concentrated in vacuo the residue purified by flash chromatography (30% to 60% ethyl acetate in hexanes)

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 4-(chloromethyl)-4-methyloxazolidin-2-one (1.49 g, 9.96 mmol) in DMF (100 ml) was added sodium bromide (11.02 g, 107 mmol), and the suspension heated to 80° C. for 6 h. The suspension was concentrated in vacuo and the residue purified by flash chromatography (30% to 60% ethyl acetate in hexanes) to give the title compound as a white solid (1.33 g, 6.86 mmol, 66%). 1H NMR (CDCl3, 400 MHz) δ 1.54 (s, 3H), 3.47 (s, 2H), 4.14 (d, J=9.2 Hz, 1H), 4.35 (d, J=8.8 Hz, 1H), 6.24 (br s, 1H). LRMS (ESI/APCI): 194 [M+H]+. The suspension was concentrated in vacuo the residue purified by flash chromatography (30% to 60% ethyl acetate in hexanes)

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

Procedure: A solution of 4-(chloromethyl)-4-methyloxazolidin-2-one (2.70 g, 18.1 mmol) in 1.0 M NaOH (20 ml) was cooled to 0° C. Bromine (1.0 ml, 20 mmol) was added dropwise, and stirred for 30 min. The precipitate was filtered off to give the title compound (2.32 g, 10.2 mmol, 56%). 1H NMR (CDCl3, 400 MHz) δ 1.44 (s, 3H), 3.49 (d, J=12.0 Hz, 1H), 3.65 (d, J=12.0 Hz, 1H), 4.22 (d, J=8.8 Hz, 1H), 4.57 (d, J=8.4 Hz, 1H). LRMS (ESI/APCI): 228 [M+H]+. The precipitate was filtered off

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

Procedure: A solution of 4-(chloromethyl)-4-methyloxazolidin-2-one (13.39 g, 89.52 mmol) in MeOH (100 ml) was cooled to 0° C., and tert-butylhypochlorite (12.0 ml, 101 mmol) was added dropwise over 15 min. The solution was warmed to RT over 45 min, and concentrated in vacuo. The residue was crystallized by dissolution in ˜80 ml CH2Cl2 followed by careful layering of 60 ml hexanes to afford the title compound as white, fan-shaped crystals (12.31 g, 66.89 mmol, 75%). 1H NMR (CDCl3, 400 MHz) δ1.50 (s, 3H), 3.55 (d, J=12.0 Hz, 1H), 3.75 (d, J=12.0 Hz, 1H), 4.19 (d, J=8.8 Hz, 1H), 4.53 (d, J=8.4 Hz, 1H). 13C NMR (CDCl3, 100 MHz) δ 20.4, 46.7, 64.1, 155.7. LRMS (ESI/APCI): 225 [M+H+CH3CN]+, 191 [M+H−Cl+CH3CN]+, 184 [M+H]+, 150 [M+H−Cl]+. concentrated in vacuo The residue was crystallized by dissolution in ˜80 ml CH2Cl2

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

Procedure: To a suspension of 4-(hydroxymethyl)-4-methyloxazolidin-2-one (1.89 g, 14.4 mmol) in 1,2-dichloroethane (10 ml) was added thionyl chloride (5.0 ml, 69 mmol). The solution was stirred for 30 min at RT, and then pyridine (5.0 ml, 62 mmol) was added. The solution was heated to 90° C. for 16 h and then 110° C. for an additional 2 h, then cooled to RT and evaporated. The residue was purified by flash chromatography (30% to 100% ethyl acetate in hexanes, Rf=0.25 in 1:1 ethyl acetate:hexanes) to give the title compound as a clear oil which solidified to a white solid upon standing (1.52 g, 10.2 mmol, 71%). 1H NMR (CDCl3, 400 MHz) δ 1.49 (s, 3H), 3.55 (m, 2H), 4.12 (d, 1H, J=9.2 Hz), 4.31 (d, 1H, J=8.8 Hz), 5.4 (br s, 1H). LRMS (ESI/APCI): 150 [M+H]+. The solution was heated to 90° C. for 16 h 110° C. for an additional 2 h cooled to RT evaporated The residue was purified by flash chromatography (30% to 100% ethyl acetate in hexanes, Rf=0.25 in 1:1 ethyl acetate:hexanes)

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

Procedure: To a suspension of 4-(hydroxymethyl)-4-methyloxazolidin-2-one (1.89 g, 14.4 mmol) in 1,2-dichloroethane (10 ml) was added thionyl chloride (5.0 ml, 69 mmol). The solution was stirred for 30 min at RT, and then pyridine (5.0 ml, 62 mmol) was added. The solution was heated to 90° C. for 16 h and then 110° C. for an additional 2 h, then cooled to RT and evaporated. The residue was purified by flash chromatography (30% to 100% ethyl acetate in hexanes, Rf=0.25 in 1:1 ethyl acetate:hexanes) to give the title compound as a clear oil which solidified to a white solid upon standing (1.52 g, 10.2 mmol, 71%). 1H NMR (CDCl3, 400 MHz) δ 1.49 (s, 3H), 3.55 (m, 2H), 4.12 (d, 1H, J=9.2 Hz), 4.31 (d, 1H, J=8.8 Hz), 5.4 (br s, 1H). LRMS (ESI/APCI): 150 [M+H]+. The solution was heated to 90° C. for 16 h 110° C. for an additional 2 h cooled to RT evaporated The residue was purified by flash chromatography (30% to 100% ethyl acetate in hexanes, Rf=0.25 in 1:1 ethyl acetate:hexanes)

Conditions: temp:85.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 4-(chloromethyl)-4-methyloxazolidin-2-one (1.41 g, 9.43 mmol) in THF (40 ml) was added pyrrolidine (5.0 ml, 61 mmol) and sodium iodide (1.03 g, 6.87 mmol). The solution was sealed, heated to 85° C. for 24 h, cooled to RT, filtered, and concentrated in vacuo. Flash chromatography (2%→12% MeOH in CH2Cl2) afforded the oxazolidinone (609.8 mg, 3.31 mmol, 35%) as a brown oil which solidified upon standing. The dihydrooxazole was isolated in roughly 75% purity (1.8 g crude yield) and was characterized only by MS. 1H NMR (CDCl3, 400 MHz) δ 1.35 (s, 3H), 1.7-1.8 (m, 4H), 2.5-2.7 (m, 6H), 4.02 (d, J=8.4 Hz, 1H), 4.24 (d, J=8.4 Hz, 1H), 5.3-5.4 (br s, 1H). ESI/APCI expected for C9H16N2O2: 184.12. Found: 185 (MH+). 1H NMR (CDCl3, 400 MHz) δ 1.35 (s, 3H), 1.7-1.8 (m, 4H), 2.5-2.7 (m, 6H), 4.02 (d, J=8.4 Hz, 1H), 4.24 (d, J=8.4 Hz, 1H), 5.3-5.4 (br s, 1H). ESI/APCI expected for C9H16N2O2: 184.12. Found: 185 (MH+). The solution was sealed cooled to RT filtered concentrated in vacuo

Conditions: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 4-(chloromethyl)-4-methyloxazolidin-2-one (1.85 g, 12.4 mmol) in DMF (5 ml) was added 1,2-ethanedithiol (10.0 ml, 119 mmol). Triethylamine (2.0 ml, 14 mmol) was added, and the solution heated to 90° C. for 2 h, then cooled to RT and concentrated in vacuo. Purification of the residue by flash chromatography (30%→80% EtOAc in hexanes) afforded a mixture of the title compound and various EDT disulfide adducts which was used without further purification. ESI/APCI expected for C7H13NO2S2: 207.04. Found: 208 (MH+), 300 (MH++EDT), 414 (MNa++2 EDT). cooled to RT concentrated in vacuo Purification of the residue by flash chromatography (30%→80% EtOAc in hexanes) afforded

Conditions: temp:110.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a suspension of 4-(hydroxymethyl)-4-methyloxazolidin-2-one (1.89 g, 14.4 mmol) in 1,2-dichloroethane (10 ml) was added thionyl chloride (5.0 ml, 69 mmol) dropwise over 10 min. Pyridine (5.0 ml, 62 mmol) was added, and the solution heated to 110° C. for 2 h. The solution was cooled to RT, concentrated, and the residue purified by flash chromatography (30%→100% EtOAc in hexanes) to give the title compound as a white solid (1.52 g, 10.2 mmmol, 71%). 1H NMR (CDCl3, 400 MHz) δ 1.49 (s, 3H), 3.55 (s, 2H), 4.12 (d, J=9.2 Hz, 1H), 4.33 (d, 8.8 Hz, 1H), 5.8 (br s, 1H). ESI/APCI calculated for C5H8ClNO2: 149.02. Found: 150 (MH+). The solution was cooled to RT concentrated the residue purified by flash chromatography (30%→100% EtOAc in hexanes)

Conditions: temp:110.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a suspension of 4-(hydroxymethyl)-4-methyloxazolidin-2-one (1.89 g, 14.4 mmol) in 1,2-dichloroethane (10 ml) was added thionyl chloride (5.0 ml, 69 mmol) dropwise over 10 min. Pyridine (5.0 ml, 62 mmol) was added, and the solution heated to 110° C. for 2 h. The solution was cooled to RT, concentrated, and the residue purified by flash chromatography (30%→100% EtOAc in hexanes) to give the title compound as a white solid (1.52 g, 10.2 mmmol, 71%). 1H NMR (CDCl3, 400 MHz) δ 1.49 (s, 3H), 3.55 (s, 2H), 4.12 (d, J=9.2 Hz, 1H), 4.33 (d, 8.8 Hz, 1H), 5.8 (br s, 1H). ESI/APCI calculated for C5H8ClNO2: 149.02. Found: 150 (MH+). The solution was cooled to RT concentrated the residue purified by flash chromatography (30%→100% EtOAc in hexanes)

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

Procedure: A solution of 4-(chloromethyl)-4-methyloxazolidin-2-one (2.97 g, 19.9 mmol) in 2.0 M dimethylamine in THF (50 ml, 100 mmol) in a sealed tube was heated to 85° C. for 24 h, cooled to RT, and filtered through a coarse glass filter to remove precipitated dimethylammonium chloride. The filtrate was concentrated, and the residue purified by flash chromatography (3%→10% MeOH in CH2Cl2) to afford the oxazolidinone as a brown oil (1.02 g, 6.45 mmol, 32%), and the dihydrooxazole as a yellow oil (1.62 g, 10.2 mmol, 52%). Rf=0.5 in 10% MeOH in CH2Cl2. 1H NMR (CDCl3, 400 MHz) δ 1.35 (s, 3H), 2.33 (s, 6H), 2.37 (d, J=13.6 Hz, 1H), 2.43 (d, J=14.4 Hz, 1H), 4.02 (d, J=8.4 Hz, 1H), 4.18 (d, J=8.4 Hz, 1H), 5.2 (br s, 1H). ESI/APCI expected for C7H14N2O2: 158.11. Found: 159 (MH+). filtered through a coarse glass filter to remove precipitated dimethylammonium chloride The filtrate was concentrated the residue purified by flash chromatography (3%→10% MeOH in CH2Cl2)

Conditions: temp:110.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a suspension of 4-(hydroxymethyl)-4-methyloxazolidin-2-one (1.89 g, 14.4 mmol) in 1,2-dichloroethane (10 ml) was added thionyl chloride (5.0 ml, 69 mmol) dropwise over 10 min. Pyridine (5.0 ml, 62 mmol) was added, and the solution heated to 110° C. for 2 h. The solution was cooled to RT, concentrated, and the residue purified by flash chromatography (30%→100% EtOAc in hexanes) to give the title compound as a white solid (1.52 g, 10.2 mmmol, 71%). 1H NMR (CDCl3, 400 MHz) δ 1.49 (s, 3H), 3.55 (s, 2H), 4.12 (d, J=9.2 Hz, 1H), 4.33 (d, 8.8 Hz, 1H), 5.8 (br s, 1H). ESI/APCI calculated for C5H8ClNO2: 149.02. Found: 150 (MH+). The solution was cooled to RT concentrated the residue purified by flash chromatography (30%→100% EtOAc in hexanes)