carbonochloridoyloxymethyl acetate

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred suspension of the 4-{4-[(5S)-5-(aminomethyl)-2-oxo-1,3-oxazolidin-3-yl]-2-fluorophenyl}tetrahydro-1λ6-thiopyran-1,1(2H)-dione (4.68 g, 13.74 mmol) prepared according to the PCT international publication WO 97/09328 in CH2Cl2 (100 mL) cooled to 0° C. is added diisopropylethylamine (4.8 ml, 27.48 mmol) followed by a solution of 2.4 g (1.5 7 mmol) of the acid chloride (from Step 4) in CH2Cl2 (10 mL) with a 2 mL rinse. The reaction mixture is stirred at 0° C. fro 30 min then at RT for 3 h. The reaction mixture is partitioned between CH2Cl2 (300 mL) and H2O (200 mL). The phases are separated. The organics are washed with 1N HCl (100 mL), brine (100 mL), dried (MgSO4), filtered and concentrated. The residue is dissolved in CH2Cl2, absorbed onto silca gel and purified on a Biotage 40M with a SIM using 2% CH3OH in CH2Cl2 as the eluent to afford 5.32 g (11.6 mmol, 85%) of the desired carbamate as a white foam. 1H NMR (DMSO) δ 7.96 (t, J=6 Hz, 1H), 7.48 (dd, J=14, 2 Hz, 1H), 7.38 (t, J=9 Hz, 1H), 7.24 (dd, J=9, 2 Hz, 1H), 5.61(s, 2H), 4.74 (m, 1H), 4.12 (t, J=9 Hz, 1H), 3.76 (dd, J=9, 7 Hz, 1H), 3.38 (m, 4 H), 3.16 (m, 1H), 3.11 (m, 2H), 2.13 (m, 2H), 2.06 (m, 1H), 2.01 (s, 3H); 13C NMR (DMSO-d6) δ 169.3, 160.6, 158 (d, J=246 Hz), 154.8, 153.8, 138.3 (d, J=8 Hz), 128.1, 125.2 (d, J=11 Hz), 113.7, 105.2 (d, J=26 Hz), 79.3, 71.7, 54.8, 50.3, 46.8, 43.1, 33.3, 29.8, 20.4; IR (diffuse reflectance) 2415, 2351, 2328, 1921, 1916, 1753, 1744, 1515, 1411, 1292, 1247, 1223, 1121, 1010, 983 cm−1. % Water (KF titration): 1.08. [a]25D=−36° (c 0.91, DMSO). Anal. Calcd for C19H23FN2O8S plus 1.08% H2O: C, 49.24; H, 5.12; N, 6.04; S, 6.85. Found: C, 49.05; H, 5.21; N, 5.81; S, 6.85. prepared rinse at RT for 3 h The reaction mixture is partitioned between CH2Cl2 (300 mL) and H2O (200 mL) The phases are separated The organics are washed with 1N HCl (100 mL), brine (100 mL) dried (MgSO4) filtered concentrated The residue is dissolved in CH2Cl2 absorbed onto silca gel purified on a Biotage 40M with a SIM

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred suspension of the 4-{4-[(5S)-5-(aminomethyl)-2-oxo-1,3-oxazolidin-3-yl]-2-fluorophenyl}tetrahydro-1λ6-thiopyran-1,1(2H)-dione (4.68 g, 13.74 mmol) prepared according to the PCT international publication WO 97/09328 in CH2Cl2 (100 mL) cooled to 0° C. is added diisopropylethylamine (4.8 ml, 27.48 mmol) followed by a solution of 2.4 g (1.5 7 mmol) of the acid chloride (from Step 4) in CH2Cl2 (10 mL) with a 2 mL rinse. The reaction mixture is stirred at 0° C. fro 30 min then at RT for 3 h. The reaction mixture is partitioned between CH2Cl2 (300 mL) and H2O (200 mL). The phases are separated. The organics are washed with 1N HCl (100 mL), brine (100 mL), dried (MgSO4), filtered and concentrated. The residue is dissolved in CH2Cl2, absorbed onto silca gel and purified on a Biotage 40M with a SIM using 2% CH3OH in CH2Cl2 as the eluent to afford 5.32 g (11.6 mmol, 85%) of the desired carbamate as a white foam. 1H NMR (DMSO) δ 7.96 (t, J=6 Hz, 1H), 7.48 (dd, J=14, 2 Hz, 1H), 7.38 (t, J=9 Hz, 1H), 7.24 (dd, J=9, 2 Hz, 1H), 5.61(s, 2H), 4.74 (m, 1H), 4.12 (t, J=9 Hz, 1H), 3.76 (dd, J=9, 7 Hz, 1H), 3.38 (m, 4 H), 3.16 (m, 1H), 3.11 (m, 2H), 2.13 (m, 2H), 2.06 (m, 1H), 2.01 (s, 3H); 13C NMR (DMSO-d6) δ 169.3, 160.6, 158 (d, J=246 Hz), 154.8, 153.8, 138.3 (d, J=8 Hz), 128.1, 125.2 (d, J=11 Hz), 113.7, 105.2 (d, J=26 Hz), 79.3, 71.7, 54.8, 50.3, 46.8, 43.1, 33.3, 29.8, 20.4; IR (diffuse reflectance) 2415, 2351, 2328, 1921, 1916, 1753, 1744, 1515, 1411, 1292, 1247, 1223, 1121, 1010, 983 cm−1. % Water (KF titration): 1.08. [a]25D=−36° (c 0.91, DMSO). Anal. Calcd for C19H23FN2O8S plus 1.08% H2O: C, 49.24; H, 5.12; N, 6.04; S, 6.85. Found: C, 49.05; H, 5.21; N, 5.81; S, 6.85. prepared rinse at RT for 3 h The reaction mixture is partitioned between CH2Cl2 (300 mL) and H2O (200 mL) The phases are separated The organics are washed with 1N HCl (100 mL), brine (100 mL) dried (MgSO4) filtered concentrated The residue is dissolved in CH2Cl2 absorbed onto silca gel purified on a Biotage 40M with a SIM

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To the thioester from Step 3 (2.50 g, 14.0 mmol) cooled to 0° C. is added sulfuryl chloride (1.5 mL, 18.25 mmol) over 2 min. The reaction mixture is stirred at 0° C. for 30 min then at RT for 2.5 h. The reaction mixture is concentrated and then dried on house vacuum overnight to afford 2.4 g of the desired crude product, which is used without further purification. 1H NMR (CDCl3) δ 5.83 (s, 2H), 2.19 (s, 3H); at RT for 2.5 h The reaction mixture is concentrated dried on house vacuum overnight

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

Procedure: To a solution of acetoxymethyl chloroformate (1.00 g, 0.0066 mol) and 2-hydroxyethyl methacrylate (0.86 g, 0.0066 mol) in methylene chloride (30 ml), pyridine (0.52 g, 0.0066 mol) was added at 0° C. After 10 min at 0° C. and 18 hours at 25° C. the reaction mixture was washed with aqueous hydrochloric acid (100 ml), aqueous saturated sodium hydrogen carbonate (100 ml) and water (100 ml). The solvent was removed under reduced pressure after drying (MgSO4). Flash chromatography (silicagel, hexane/ethyl acetate (3:2)) gave 1.05 g (65%) of the title product. 18 hours at 25° C. the reaction mixture was washed with aqueous hydrochloric acid (100 ml), aqueous saturated sodium hydrogen carbonate (100 ml) and water (100 ml) The solvent was removed under reduced pressure after drying (MgSO4)

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred suspension of the 4-{4-[(5S)-5-(aminomethyl)-2-oxo-1,3-oxazolidin-3-yl]-2-fluorophenyl}tetrahydro-1λ6-thiopyran-1,1(2H)-dione (4.68 g, 13.74 mmol) prepared according to the PCT international publication WO 97/09328 in CH2Cl2 (100 mL) cooled to 0° C. is added diisopropylethylamine (4.8 ml, 27.48 mmol) followed by a solution of 2.4 g (1.5 7 mmol) of the acid chloride (from Step 4) in CH2Cl2 (10 mL) with a 2 mL rinse. The reaction mixture is stirred at 0° C. fro 30 min then at RT for 3 h. The reaction mixture is partitioned between CH2Cl2 (300 mL) and H2O (200 mL). The phases are separated. The organics are washed with 1N HCl (100 mL), brine (100 mL), dried (MgSO4), filtered and concentrated. The residue is dissolved in CH2Cl2, absorbed onto silca gel and purified on a Biotage 40M with a SIM using 2% CH3OH in CH2Cl2 as the eluent to afford 5.32 g (11.6 mmol, 85%) of the desired carbamate as a white foam. 1H NMR (DMSO) δ 7.96 (t, J=6 Hz, 1H), 7.48 (dd, J=14, 2 Hz, 1H), 7.38 (t, J=9 Hz, 1H), 7.24 (dd, J=9, 2 Hz, 1H), 5.61(s, 2H), 4.74 (m, 1H), 4.12 (t, J=9 Hz, 1H), 3.76 (dd, J=9, 7 Hz, 1H), 3.38 (m, 4 H), 3.16 (m, 1H), 3.11 (m, 2H), 2.13 (m, 2H), 2.06 (m, 1H), 2.01 (s, 3H); 13C NMR (DMSO-d6) δ 169.3, 160.6, 158 (d, J=246 Hz), 154.8, 153.8, 138.3 (d, J=8 Hz), 128.1, 125.2 (d, J=11 Hz), 113.7, 105.2 (d, J=26 Hz), 79.3, 71.7, 54.8, 50.3, 46.8, 43.1, 33.3, 29.8, 20.4; IR (diffuse reflectance) 2415, 2351, 2328, 1921, 1916, 1753, 1744, 1515, 1411, 1292, 1247, 1223, 1121, 1010, 983 cm−1. % Water (KF titration): 1.08. [a]25D=−36° (c 0.91, DMSO). Anal. Calcd for C19H23FN2O8S plus 1.08% H2O: C, 49.24; H, 5.12; N, 6.04; S, 6.85. Found: C, 49.05; H, 5.21; N, 5.81; S, 6.85. prepared rinse at RT for 3 h The reaction mixture is partitioned between CH2Cl2 (300 mL) and H2O (200 mL) The phases are separated The organics are washed with 1N HCl (100 mL), brine (100 mL) dried (MgSO4) filtered concentrated The residue is dissolved in CH2Cl2 absorbed onto silca gel purified on a Biotage 40M with a SIM

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To the thioester from Step 3 (2.50 g, 14.0 mmol) cooled to 0° C. is added sulfuryl chloride (1.5 mL, 18.25 mmol) over 2 min. The reaction mixture is stirred at 0° C. for 30 min then at RT for 2.5 h. The reaction mixture is concentrated and then dried on house vacuum overnight to afford 2.4 g of the desired crude product, which is used without further purification. 1H NMR (CDCl3) δ 5.83 (s, 2H), 2.19 (s, 3H); at RT for 2.5 h The reaction mixture is concentrated dried on house vacuum overnight