60% |
With pyridine; at 0 - 20℃; for 2h;Product distribution / selectivity; |
A solution of /?-toluenesulfonyl chloride (24.8 g, 130 mmol) in pyridine (150 mL) was added to a stirred solution of isomannide (40) (19.0 g, 130 mmol) in pyridine (150 mL) over 1 hour at 0 0C then stirred at ambient temperature for 1 hour. The mixture was poured onto iced- water (1 L) then extracted with dichloromethane (3 x 300 mL). The organic phase washed with brine (300 mL), dried (MgSO4), filtered and reduced in vacuo to leave a residue. Flash chromatography over silica, eluting with ethyl acetate : heptane mixtures 0 : 100 to 50 : 50 gave monotosylate (50) (23.4 g, 60%) as a white solid. |
60% |
With pyridine; at 0 - 20℃; for 2h;Product distribution / selectivity; |
Alternative preparation of (3R, 3&S, 6R, 6a/O-6-Hvdroxyhexahydrofuro|3,2- Mfuran-3-yl 4-methylbenzenesulfonate (50). A solution of />-toluenesulfonyl chloride (24.8 g, 130 mmol) in pyridine (150 mL) was added to a stirred solution of isomannide (40) (19.0 g, 130 mmol) in pyridine (150 mL) over 1 hour at 0 0C then stirred at ambient temperature for 1 hour. The mixture was poured onto iced- water (1 L) then extracted with dichloromethane (3 x 300 mL). The organic phase washed with brine (300 mL), dried (MgSO4), filtered and reduced in vacuo to leave a residue. Flash chromatography over silica, eluting with ethyl acetate : heptane mixtures 0 : 100 to 50 : 50 gave monotosylate (50) (23.4 g, 60%) as a white solid. |
60% |
With pyridine; at 0 - 20℃; for 2h;Product distribution / selectivity; |
A solution of /?-toluenesulfonyl chloride (24.8 g, 130 mmol) in pyridine (150 mL) was added to a stirred solution of isomannide (40) (19.0 g, 130 mmol) in pyridine (150 mL) over 1 hour at 0 C then stirred at ambient temperature for 1 hour. The mixture was poured onto iced- water (1 L) then extracted with dichloromethane (3 x 300 mL). The organic phase washed with brine (300 mL), dried (MgSO4), filtered and reduced in vacuo to leave a residue. Flash chromatography over silica, eluting with ethyl acetate : heptane mixtures 0 : 100 to 50 : 50 gave monotosylate (50) (23.4 g, 60%) as a white solid. |
60% |
With pyridine; at 0 - 20℃; for 2h;Product distribution / selectivity; |
A solution of /7-toluenesulfonyl chloride (24.8 g, 130 mmol) in pyridine (150 mL) was added to a stirred solution of isomannide (40) (19.0 g, 130 mmol) in pyridine (150 mL) over 1 hour at 0 C then stirred at ambient temperature for 1 hour. The mixture was poured onto iced-water (1L) then extracted with dichloromethane (3 x 300 mL). The organic phase washed with brine (300 mL), dried (MgSO4), filtered and reduced in vacuo to leave a residue. Flash <n="104"/>chromatography over silica, eluting with ethyl acetate : heptane mixtures 0 : 100 to 50 :50 gave monotosylate (50) (23.4 g, 60%) as a white solid. |
38% |
With potassium hydroxide; In tetrachloromethane; dichloromethane; water; at 0℃; for 7.5h;Product distribution / selectivity; |
Isomannide (40) (10 g, 68.49 mmol) and p- toluenesulphonyl chloride (6.53 g, 34.25 mmol) were dissolved in a mixture of carbon tetrachloride (50 mL), dichloromethane (5 mL) and water (40 niL). The flask was cooled to 0 C and a solution of potassium hydroxide (1.92 g, 34.25 mmol) in water (5 mL) added drop wise over 30 minutes with stirring. The resulting biphasic mixture was stirred at 0 C for 7 hours. Then off-white precipitate was collected by filtration in vacuo then partitioned between dichloromethane (30 mL) and water (10 mL). The organic phase was washed with brine (2 x 10 mL) then dried (Na2SO4), filtered and reduced in vacuo to leave a colourless solid. Recrystallisation from carbon tetrachloride gave monotosylate (50) as colourless granules (3.92 g, 38%). TLC (R/ = 0.11, EtOAc : heptane 1 : 1); analytical HPLC main peak, Rt = 10.692 min; HPLC-MS 318.2, 323.1 [M + Na]+, 623.2 [2M + Na]+; [alpha] ^s+72.2 (c = 5.4, CHCl3); deltaH (500 MHz, CDCl3) 2.44 (3H, s, CH3), 3.54 (IH, dd, J= 9.31 and 7.23 Hz, OCH2CHOH), 3.78 (IH, dd, J= 9.18 and 7.59 Hz, OCH2CHOTs), 3.95 (IH, dd, J = 9.36 and 6.45 Hz, OCH2CHOH), 4.01 (IH, dd, J = 9.33 and 6.64 Hz, OCH2CHOTs), 4.26 (IH, m, CHOH), 4.42 and 4.48 (each IH, brt, J = 5.03 and 5.00 Hz respectively, CHCHCHOH and CHCHCHOTs), 4.90 (IH, dd, J= 12.15 and 6.84 Hz, CHOTs), 7.37 (2eta, d, J= 8.13 Hz, aromatic CH3CCH), 7.82 (2eta, d, J= 8.20 Hz, aromatic OSO2CCH); deltac (125 MHz, CDCl3) 21.69 (CH3), 70.03 (CH2CHOTs), 72.29 (CHOTs), 74.02 (CH2CHOH), 80.00 (CH2CHOH), 81.36 (CHCHOTs), 81.76 (CHCHOH), 128.00 and 129.89 (aromatic CH), 133.04 (CHOSO2C quaternary), 145.26 (CH3C quaternary). |
38% |
With potassium hydroxide; In tetrachloromethane; dichloromethane; water; at 0℃; for 7.5h;Product distribution / selectivity; |
Isomannide (40) (10 g, 68.49 mmol) and p- toluenesulphonyl chloride (6.53 g, 34.25 mmol) were dissolved in a mixture of carbon tetrachloride (50 mL), dichloromethane (5 mL) and water (40 mL). The flask was cooled to 0 C and a solution of potassium hydroxide (1.92 g, 34.25 mmol) in water (5 mL) added dropwise over 30 minutes with stirring. The resulting biphasic mixture was stirred at 0 C for 7 hours. Then off-white precipitate was collected by filtration in vacuo then partitioned between dichloromethane (30 mL) and water (10 mL). The organic phase was washed with brine (2 x 10 mL) then dried (Na2SO4), filtered and reduced in vacuo to leave a colourless solid. Recrystallisation from carbon tetrachloride gave monotosylate (50) as colourless granules (3.92 g, 38%). TLC (Rf= 0.11, EtOAc : heptane 1 : 1); analytical HPLC main peak, R, = 10.692 min; HPLC-MS 318.2, 323.1 [M + Na]+, 623.2 [2M + Na]+; [alpha] 'D8+72.2 (c = 5.4, CHCl3); deltaH (500 MHz, CDCl3)2.44 (3H, s, CH3), 3.54 (1eta, dd, J- 9.31 and 7.23 Hz, OCH2CHOH), 3.78 (IH, dd, J = 9.18 and 7.59 Hz, OCH2CHOTs), 3.95 (IH, dd, J = 9.36 and 6.45 Hz, OCH2CHOH), 4.01 (IH, dd, J = 9.33 and 6.64 Hz, OCH2CHOTs), 4.26 (IH, m, CHOH), 4.42 and 4.48 (each IH, bit, J = 5.03 and 5.00 Hz respectively, CHCHCHOH and CHCHCHOTs), 4.90 (IH, dd, J = 12.15 and 6.84 Hz, CHOTs), 7.37 (2eta, d, J = 8.13 Hz, aromatic CH3CCH), 7.82 (2eta, d, J= 8.20 Hz, aromatic OSO2CCH); deltac (125 MHz, CDCl3) 21.69 (CH3), 70.03 (CH2CHOTs), 72.29 (CHOTs), 74.02 (CH2CHOH), 80.00 (CH2CHOH), 81.36 (CHCHOTs), 81.76 (CHCHOH), 128.00 and 129.89 (aromatic CH), 133.04 (CHOSO2C quaternary), 145.26 (CH3C quaternary). |
38% |
With potassium hydroxide; In tetrachloromethane; dichloromethane; water; at 0℃; for 7.5h;Product distribution / selectivity; |
Isomannide (40) (10 g, 68.49 mmol) and p- toluenesulphonyl chloride (6.53 g, 34.25 mmol) were dissolved in a mixture of carbon tetrachloride (50 mL), dichloromethane (5 mL) and water (40 mL). The flask was cooled to 0 0C and a solution of potassium hydroxide (1.92 g, 34.25 mmol) in water (5 mL) added dropwise over 30 minutes with stirring. The resulting biphasic mixture was stirred at 0 0C for 7 hours. Then off-white precipitate was collected by filtration in vacuo then partitioned between dichloromethane (30 mL) and water (10 mL). The organic phase was washed with brine (2 x 10 mL) then dried (Na2SO4), filtered and <n="125"/>reduced in vacuo to leave a colourless solid. Recrystallisation from carbon tetrachloride gave monotosylate (50) as colourless granules (3.92 g, 38%). TLC (Rf= OA l, EtOAc : heptane 1 : 1); analytical HPLC main peak, R, = 10.692 min; HPLC-MS 318.2, 323.1 [M + Na]+, 623.2 [2M + Na]+; [alpha] ^8 +72.2 (c = 5.4, CHCl3); deltaH (500 MHz, CDCl3) 2.44 (3H, s, CH3), 3.54 (1eta, dd, J= 9.31 and 7.23 Hz, OCH2CHOH), 3.78 (IH, dd, J = 9.18 and 7.59 Hz, OCH2CHOTs), 3.95 (IH, dd, J = 9.36 and 6.45 Hz, OCH2CHOH), 4.01 (IH, dd, J = 9.33 and 6.64 Hz, OCH2CHOTs), 4.26 (IH, m, CHOH), 4.42 and 4.48 (each IH, brt, J = 5.03 and 5.00 Hz respectively, CHCHCHOH and CHCHCHOTs), 4.90 (IH, dd, J= 12.15 and 6.84 Hz, CHOTs), 7.37 (2eta, d, J = 8.13 Hz, aromatic CH3CCH), 7.82 (2eta, d, J= 8.20 Hz, aromatic OSO2CCH); deltac (125 MHz, CDCl3) 21.69 (CH3), 70.03 (CH2CHOTs), 72.29 (CHOTs), 74.02 (CH2CHOH), 80.00 (CH2CHOH), 81.36 (CHCHOTs), 81.76 (CHCHOH), 128.00 and 129.89 (aromatic CH), 133.04 (CHOSO2C quaternary), 145.26 (CH3C quaternary). |
38% |
With potassium hydroxide; In tetrachloromethane; dichloromethane; water; at 0℃; for 7.5h;Product distribution / selectivity; |
Preparation of (3R, 3aS, 6R, 6aJ?)-6-Hvdroxyhexahvdrofurof3,2-Alfuran-3-yl 4- methylbenzenesulfonate (50). Isomannide (40) (10 g, 68.49 mmol) and p- toluenesulphonyl chloride (6.53 g, 34.25 mmol) were dissolved in a mixture of carbon tetrachloride (50 mL), dichloromethane (5 mL) and water (40 mL). The flask was cooled to 0 0C and a solution of potassium hydroxide (1.92 g, 34.25 mmol) in water (5 mL) added dropwise over 30 minutes with stirring. The resulting biphasic mixture was stirred at 0 C for 7 hours. Then off-white precipitate was collected by filtration in vacuo then partitioned between dichloromethane (30 mL) and water (10 mL). The organic phase was washed with brine (2 x 10 mL) then dried (Na2SO4), filtered and reduced in vacuo to leave a colourless solid. Recrystallisation from carbon tetrachloride <n="90"/>gave monotosylate (50) as colourless granules (3.92 g, 38%). TLC (Rf= 0.11, EtOAc : heptane 1 : 1); analytical HPLC main peak, R1 = 10.692 min; HPLC-MS 318.2, 323.1 [M + Na]+, 623.2 [2M + Na]+; [alpha] " +72.2 (c = 5.4, CHCl3); deltaH (500 MHz, CDCl3) 2.44 (3H, s, CH3), 3.54 (IH, dd, J= 9.31 and 7.23 Hz, OCH2CHOH), 3.78 (IH, dd, J= 9.18 and 7.59 Hz, OCH2CHOTs), 3.95 (IH, dd, J = 9.36 and 6.45 Hz, OCH2CHOH), 4.01 (IH, dd, J = 9.33 and 6.64 Hz, OCH2CHOTs)5 4.26 (IH, m, CHOH), 4.42 and 4.48 (each IH, brt, J = 5.03 and 5.00 Hz respectively, CHCHCHOH and CHCHCHOTs), 4.90 (IH, dd, J = 12.15 and 6.84 Hz, CHOTs), 7.37 (2eta, d, J = 8.13 Hz, aromatic CH3CCH), 7.82 (2eta, d, J= 8.20 Hz, aromatic OSO2CCH); deltac (125 MHz, CDCl3) 21.69 (CH3), 70.03 (CH2CHOTs), 72.29 (CHOTs), 74.02 (CH2CHOH), 80.00 (CH2CHOH), 81.36 (CHCHOTs), 81.76 (CHCHOH), 128.00 and 129.89 (aromatic CH), 133.04 (CHOSO2C quaternary), 145.26 (CH3C quaternary). |
38% |
With potassium hydroxide; In tetrachloromethane; dichloromethane; water; at 0℃; for 7.5h;Product distribution / selectivity; |
Isomannide (40) (10 g, 68.49 mmol) and p- toluenesulphonyl chloride (6.53 g, 34.25 mmol) were dissolved in a mixture of carbon tetrachloride (50 mL), dichloromethane (5 mL) and water (40 mL). The flask was cooled to 0 0C and a solution of potassium hydroxide (1.92 g, 34.25 mmol) in water (5 mL) added dropwise over 30 minutes with stirring. The resulting biphasic mixture was stirred at 0 C for 7 hours. Then off-white precipitate was collected by filtration in <n="71"/>vacuo then partitioned between dichloromethane (30 mL) and water (10 mL). The organic phase was washed with brine (2 x 10 mL) then dried (Na2SO4), filtered and reduced in vacuo to leave a colourless solid. Recrystallisation from carbon tetrachloride gave monotosylate (50) as colourless granules (3.92 g, 38%). TLC (Rf= 0.11, EtOAc : heptane 1 : 1); analytical HPLC main peak, R1 = 10.692 min; HPLC-MS 318.2, 323.1[M + Na]+, 623.2 [2M + Na]+; [alpha] 'D8+72.2 (c = 5.4, CHCl3); deltaH (500 MHz, CDCl3)2.44 (3H, s, CH3), 3.54 (1eta, dd, J= 9.31 and 7.23 Hz, OCH2CHOH), 3.78 (IH, dd, J = 9.18 and 7.59 Hz, OCH2CHOTs), 3.95 (IH, dd, J = 9.36 and 6.45 Hz, OCH2CHOH), 4.01 (IH, dd, J = 9.33 and 6.64 Hz, OCH2CHOTs), 4.26 (IH, m, CHOH), 4.42 and 4.48 (each IH, brt, J = 5.03 and 5.00 Hz respectively, CHCHCHOH and CHCHCHOTs), 4.90 (IH, dd, J = 12.15 and 6.84 Hz, CHOTs), 7.37 (2eta, d, J = 8.13 Hz, aromatic CH3CCH), 7.82 (2eta, d, J= 8.20 Hz, aromatic OSO2CCH); deltac (125 MHz, CDCl3) 21.69 (CH3), 70.03 (CH2CHOTs), 72.29 (CHOTs), 74.02 (CH2CHOH), 80.00 (CH2CHOH), 81.36 (CHCHOTs), 81.76 (CHCHOH), 128.00 and 129.89 (aromatic CH), 133.04 (CHOSO2C quaternary), 145.26 (CH3C quaternary). |