3-bromooxan-2-one

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A stirred mixture of α-bromo-δ-valerolactone (77% pure; 300 g, 1.3 mol), 4-hydroxy-3-propylbenzenecarbothioamide (229.09 g; 1.2 mol) (Example 504), and absolute ethanol (2.5 L) was gradually heated under nitrogen. A significant gas evolution occurred. When the latter had slowed, the mixture was brought to reflux. After 16 h at reflux, the mixture was cooled to rt, and then concentrated in vacuo. The residue was taken-up in 50% dichloromethane/hexanes, filtered, and the solid triturated and washed with more of the solvent mixture (700 mL total). After washing with hexanes and drying in vacuo, 207.1 g (58%) of the title compound were obtained as a yellow solid. The filtrate was concentrated in vacuo, and the residue chromatographed on silica gel to afford a thick oil containing impure product in which crystals formed. Filtration, trituration, and washing of the solid with ethanol afforded 27.6 g (234.7 g total; 66.1% yield) of opaque, pastel orange crystals, mp 152-154° C.; 1H NMR (DMSO-d6): δ 9.86 (broad exchangeable s, 1H), 7.5 (d, 1H), 7.4 (dd, 1H), 6.8 (d, 1H), 4.2 (t, 2H), 2.7 (t, 2H), 2.5 (t, 2H), 2.0 (m, 2H), 1.5 (m, 2H), 0.9 (t, 3H); LCMS: RT=3.0 min, (M+H)+ 276. was gradually heated under nitrogen to reflux After 16 h at reflux concentrated in vacuo filtered the solid triturated washed with more of the solvent mixture (700 mL total) After washing with hexanes drying in vacuo

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of ethyl ((1S)-5-{3-[4-(aminocarbonothioyl)-2-propylphenoxy]propoxy}-2,3-dihydro-1H-inden-1-yl)acetate (0.5 g, 1.1 mmol) (Example 144) and 3-bromotetrahydro-2H-pyran-2-one (1.2 g, 6.6 mmol) (Example 151) in EtOH (anhydrous, 15 mL) was heated at 70° C. for 18 h. The reaction mixture was cooled to rt, and concentrated under reduced pressure. Purification by silica gel flash chromatography (EtOAc/hexane (v/v)=1:2) gave 0.17 g (29%) of the title compound as a light yellow oil. LC-MS: RT=4.52 min, (M+H)+:536.4. concentrated under reduced pressure Purification by silica gel flash chromatography (EtOAc/hexane (v/v)=1:2)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of ethyl ((1S)-5-{3-[4-(aminocarbonothioyl)-2-propylphenoxy]propoxy}-2,3-dihydro-1H-inden-1-yl)acetate (0.5 g, 1.1 mmol) (Example 144) and 3-bromotetrahydro-2H-pyran-2-one (1.2 g, 6.6 mmol) (Example 151) in EtOH (anhydrous, 15 mL) was heated at 70° C. for 18 h. The reaction mixture was cooled to rt, and concentrated under reduced pressure. Purification by silica gel flash chromatography (EtOAc/hexane (v/v)=1:2) gave 0.17 g (29%) of the title compound as a light yellow oil. LC-MS: RT=4.52 min, (M+H)+:536.4. concentrated under reduced pressure Purification by silica gel flash chromatography (EtOAc/hexane (v/v)=1:2)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A stirred mixture of α-bromo-δ-valerolactone (77% pure; 300 g, 1.3 mol), 4-hydroxy-3-propylbenzenecarbothioamide (229.09 g; 1.2 mol) (Example 504), and absolute ethanol (2.5 L) was gradually heated under nitrogen. A significant gas evolution occurred. When the latter had slowed, the mixture was brought to reflux. After 16 h at reflux, the mixture was cooled to rt, and then concentrated in vacuo. The residue was taken-up in 50% dichloromethane/hexanes, filtered, and the solid triturated and washed with more of the solvent mixture (700 mL total). After washing with hexanes and drying in vacuo, 207.1 g (58%) of the title compound were obtained as a yellow solid. The filtrate was concentrated in vacuo, and the residue chromatographed on silica gel to afford a thick oil containing impure product in which crystals formed. Filtration, trituration, and washing of the solid with ethanol afforded 27.6 g (234.7g total; 66.1% yield) of opaque, pastel orange crystals, mp 152-154° C.; 1H NMR (DMSO-d6): δ 9.8δ (broad exchangeable s, 1H), 7.5 (d, 1H), 7.4 (dd, 1H), 6.8 (d, 1H), 4.2 (t, 2H), 2.7 (t, 2H), 2.5 (t, 2H), 2.0 (m, 2H), 1.5 (m, 2H), 0.9 (t, 3H); LCMS: RT=3.0 min, (M+H)+ 276. was gradually heated under nitrogen to reflux After 16 h at reflux concentrated in vacuo filtered the solid triturated washed with more of the solvent mixture (700 mL total) After washing with hexanes drying in vacuo

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A stirred mixture of α-bromo-δ-valerolactone (77% pure; 300 g, 1.3 mol), 4-hydroxy-3-propylbenzenecarbothioamide (229.09 g; 1.2 mol) (Example 504), and absolute ethanol (2.5 L) was gradually heated under nitrogen. A significant gas evolution occurred. When the latter had slowed, the mixture was brought to reflux. After 16 h at reflux, the mixture was cooled to rt, and then concentrated in vacuo. The residue was taken-up in 50% dichloromethane/hexanes, filtered, and the solid triturated and washed with more of the solvent mixture (700 mL total). After washing with hexanes and drying in vacuo, 207.1 g (58%) of the title compound were obtained as a yellow solid. The filtrate was concentrated in vacuo, and the residue chromatographed on silica gel to afford a thick oil containing impure product in which crystals formed. Filtration, trituration, and washing of the solid with ethanol afforded 27.6 g (234.7g total; 66.1% yield) of opaque, pastel orange crystals, mp 152-154° C.; 1H NMR (DMSO-d6): δ 9.8δ (broad exchangeable s, 1H), 7.5 (d, 1H), 7.4 (dd, 1H), 6.8 (d, 1H), 4.2 (t, 2H), 2.7 (t, 2H), 2.5 (t, 2H), 2.0 (m, 2H), 1.5 (m, 2H), 0.9 (t, 3H); LCMS: RT=3.0 min, (M+H)+ 276. was gradually heated under nitrogen to reflux After 16 h at reflux concentrated in vacuo filtered the solid triturated washed with more of the solvent mixture (700 mL total) After washing with hexanes drying in vacuo

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A stirred mixture of α-bromo-δ-valerolactone (77% pure; 300 g, 1.3 mol), 4-hydroxy-3-propylbenzenecarbothioamide (229.09 g; 1.2 mol) (Example 504), and absolute ethanol (2.5 L) was gradually heated under nitrogen. A significant gas evolution occurred. When the latter had slowed, the mixture was brought to reflux. After 16 h at reflux, the mixture was cooled to rt, and then concentrated in vacuo. The residue was taken-up in 50% dichloromethane/hexanes, filtered, and the solid triturated and washed with more of the solvent mixture (700 mL total). After washing with hexanes and drying in vacuo, 207.1 g (58%) of the title compound were obtained as a yellow solid. The filtrate was concentrated in vacuo, and the residue chromatographed on silica gel to afford a thick oil containing impure product in which crystals formed. Filtration, trituration, and washing of the solid with ethanol afforded 27.6 g (234.7 g total; 66.1% yield) of opaque, pastel orange crystals, mp 152-154° C.; 1H NMR (DMSO-d6): δ 9.86 (broad exchangeable s, 1H), 7.5 (d, 1H), 7.4 (dd, 1H), 6.8 (d, 1H), 4.2 (t, 2H), 2.7 (t, 2H), 2.5 (t, 2H), 2.0 (m, 2H), 1.5 (m, 2H), 0.9 (t, 3H); LCMS: RT=3.0 min, (M+H)+ 276. was gradually heated under nitrogen to reflux After 16 h at reflux concentrated in vacuo filtered the solid triturated washed with more of the solvent mixture (700 mL total) After washing with hexanes drying in vacuo

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of ethyl ((1S)-5-{3-[4-(aminocarbonothioyl)-2-propylphenoxy]propoxy}-2,3-dihydro-1H-inden-1-yl)acetate (0.5 g, 1.1 mmol) (Example 144) and 3-bromotetrahydro-2H-pyran-2-one (1.2 g, 6.6 mmol) (Example 151) in EtOH (anhydrous, 15 mL) was heated at 70° C. for 18 h. The reaction mixture was cooled to rt, and concentrated under reduced pressure. Purification by silica gel flash chromatography (EtOAc/hexane (v/v)=1:2) gave 0.17 g (29%) of the title compound as a light yellow oil. LC-MS: RT=4.52 min, (M+H)+:536.4. concentrated under reduced pressure Purification by silica gel flash chromatography (EtOAc/hexane (v/v)=1:2)