1-bromo-1-chloroethane

反応条件: temp:0.00; pressure:0.00; stir:

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

実験手順: To a 500 mL 3-neck round-bottom flask was added 4-chloro-3-nitro-phenol (10 g, 0.058 mol), potassium carbonate (20 g, 0.14 mol), bromochloroethane (34.5 g, 0.24 mol) and 2-butanone (200 mL). The mixture was mechanically stirred and heated to reflux for 20 hours under nitrogen then allowed to cool to room temperature and the solids were filtered. The solvent was evaporated under vacuum and the oil dissolved in diethyl ether (300 mL) and washed with 10% sodium hydroxide. The organic layer was dried over anhydrous magnesium sulfate, filtered and the solvent removed under vacuum. The product was dissolved in 1:1 methylene chloride-hexanes and filtered through a short pad silica. Upon concentration and standing 12.9 g (94.8.% %) of light yellow crystalline solid was afforded: mp 46°-48° C.; MS EI m/e 235, 237, 239 (M+); 1H NMR (400 MHz, DMSO-d6) δ 3.95 (t, 2H, J=5.2 Hz), 4.36 (t, 2H, J=5.2 Hz), 7.32 (dd, 1H, J=3.2, J=8.9 Hz), 7.66, (d, 1H, J=9 Hz), 7.69, (d, 1H, J=3.2 Hz). heated to reflux for 20 hours under nitrogen the solids were filtered The solvent was evaporated under vacuum the oil dissolved in diethyl ether (300 mL) washed with 10% sodium hydroxide The organic layer was dried over anhydrous magnesium sulfate filtered the solvent removed under vacuum The product was dissolved in 1:1 methylene chloride-hexanes filtered through a short pad silica Upon concentration was afforded

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

実験手順: To a solution of 2-methoxyphenol (14.4 g, 116 mmol) in 2-butanone (200 mL) was added bromochloroethane (69.0 g, 480 mmol) followed by the addition of potassium carbonate (40.0 g, 280 mmol). The reaction mixture was mechanically stirred and heated to reflux for 24 h, then cooled to room temperature. The solids were filtered off and the solvent was removed under vacuum. The residue was dissolved in diethyl ether and washed with 10% of NaOH, dried over anhydrous magnesium sulfate, filtered and concentrated. Purification by silica gel column chromatography (25% EtOAc/hexane) afforded 7.55 g (35%) of a solid: mp 36-38°C. (Lit.2 41-43° C,); 1H NMR (DMSO, 400 MHz), 3.75 (s, 3H), 3.91 (dd, 2H), 4.20 (dd, 2H), 6.86-6.99 (m, 4H); MS (EI) m/z 186 (M+). heated to reflux for 24 h The solids were filtered off the solvent was removed under vacuum The residue was dissolved in diethyl ether washed with 10% of NaOH dried over anhydrous magnesium sulfate filtered concentrated Purification by silica gel column chromatography (25% EtOAc/hexane)

反応条件: temp:0.00; pressure:0.00; stir:

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

実験手順: A mixture of 7,7,9,9-tetramethyl-1,3,8-triazaspiro[4.5]decane-2,4-dione (5, 22.2 mmol) and KOH (1.24 g, 22.2 mmol) in EtOH was refluxed for 10 min and bromochloroethane (6.35 g, 44.4 mmol) was added and refluxing continued for additional 6 h. Filtered and concentrated to get the crude chloroethylated product which was used as such for the next step (5.5 g). LCMS—[M+H] m/z 228. was refluxed for 10 min refluxing Filtered concentrated to get the crude chloroethylated product which

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

実験手順: To a 500 mL 3-neck round-bottom flask was added 4-chloro-3-nitro-phenol (10 g, 0.058 mol), potassium carbonate (20 g, 0.14 mol), bromochloroethane (34.5 g, 0.24 mol) and 2-butanone (200 mL). The mixture was mechanically stirred and heated to reflux for 20 hours under nitrogen then allowed to cool to room temperature and the solids were filtered. The solvent was evaporated under vacuum and the oil dissolved in diethyl ether (300 mL) and washed with 10% sodium hydroxide. The organic layer was dried over anhydrous magnesium sulfate, filtered and the solvent removed under vacuum. The product was dissolved in 1:1 methylene chloride-hexanes and filtered through a short pad silica. Upon concentration and standing 12.9 g (94.8.% %) of light yellow crystalline solid was afforded: mp 46°-48° C.; MS EI m/e 235, 237, 239 (M+); 1H NMR (400 MHz, DMSO-d6) δ 3.95 (t, 2H, J=5.2 Hz), 4.36 (t, 2H, J=5.2 Hz), 7.32 (dd, 1H, J=3.2, J=8.9 Hz), 7.66, (d, 1H, J=9 Hz), 7.69, (d, 1H, J=3.2 Hz). heated to reflux for 20 hours under nitrogen the solids were filtered The solvent was evaporated under vacuum the oil dissolved in diethyl ether (300 mL) washed with 10% sodium hydroxide The organic layer was dried over anhydrous magnesium sulfate filtered the solvent removed under vacuum The product was dissolved in 1:1 methylene chloride-hexanes filtered through a short pad silica Upon concentration was afforded

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

実験手順: To a solution of 2-methoxyphenol (14.4 g, 116 mmol) in 2-butanone (200 mL) was added bromochloroethane (69.0 g, 480 mmol) followed by the addition of potassium carbonate (40.0 g, 280 mmol). The reaction mixture was mechanically stirred and heated to reflux for 24 h, then cooled to room temperature. The solids were filtered off and the solvent was removed under vacuum. The residue was dissolved in diethyl ether and washed with 10% of NaOH, dried over anhydrous magnesium sulfate, filtered and concentrated. Purification by silica gel column chromatography (25% EtOAc/hexane) afforded 7.55 g (35%) of a solid: mp 36-38°C. (Lit.2 41-43° C,); 1H NMR (DMSO, 400 MHz), 3.75 (s, 3H), 3.91 (dd, 2H), 4.20 (dd, 2H), 6.86-6.99 (m, 4H); MS (EI) m/z 186 (M+). heated to reflux for 24 h The solids were filtered off the solvent was removed under vacuum The residue was dissolved in diethyl ether washed with 10% of NaOH dried over anhydrous magnesium sulfate filtered concentrated Purification by silica gel column chromatography (25% EtOAc/hexane)

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

実験手順: To a solution of 2-methoxyphenol (14.4 g, 116 mmol) in 2-butanone (200 mL) was added bromochloroethane (69.0 g, 480 mmol) followed by the addition of potassium carbonate (40.0 g, 280 mmol). The reaction mixture was mechanically stirred and heated to reflux for 24 h, then cooled to room temperature. The solids were filtered off and the solvent was removed under vacuum. The residue was dissolved in diethyl ether and washed with 10% of NaOH, dried over anhydrous magnesium sulfate, filtered and concentrated. Purification by silica gel column chromatography (25% EtOAc/hexane) afforded 7.55 g (35%) of a solid: mp 36-38°C. (Lit.2 41-43° C,); 1H NMR (DMSO, 400 MHz), 3.75 (s, 3H), 3.91 (dd, 2H), 4.20 (dd, 2H), 6.86-6.99 (m, 4H); MS (EI) m/z 186 (M+). heated to reflux for 24 h The solids were filtered off the solvent was removed under vacuum The residue was dissolved in diethyl ether washed with 10% of NaOH dried over anhydrous magnesium sulfate filtered concentrated Purification by silica gel column chromatography (25% EtOAc/hexane)

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

実験手順: This compound was prepared according to the procedure described by Evans, et al., J. Org. Chem. 35, 4122 (1970) for the synthesis of 3-methyl-1,2,4,5-tetrahydro-3H-benz[e]indole as follows. Into a dry, nitrogen filled, one liter 3-neck flask fitted with reflux condenser, serum cap, dropping funnel and magnetic stirrer, was added a solution of 38.55 g (167.9 mmol) XIIa in dry tetrahydrofuran (THF) (50 ml) which was placed under a slow stream of nitrogen. A 2.20 M solution of isopropyl magnesium chloride in THF (96.1 ml, 211.7 mmol) was added slowly via a syringe at such a rate as to maintain gentle reflux. After the addition (15 min), 30.72 g (214.2 mmol) of bromochloroethan was added to the warm reaction mixture at a rate sufficient to maintain gentle refluxing. After the addition of the alkylhalide, an additional 52.3 ml (115 mmol) of the Grignard reagent was added to the reaction again at a controlled rate. The reaction mixture was cooled in an ice-bath and 270 ml of 1 M aqueous solution of ethylenediaminetetraacetic acid tetrasodium salt was added slowly (with stirring) and then 600 ml of a 1:1 ether-benzene was added. The organic layer was separated and the aqueous phase was extracted with ether. The combined extracts were washed with water (2×100 ml) and dried (MgSO4). Removal of the solvent by evaporation gave 43.0 g (99%) of XIIIa as a pale yellow oxygen-sensitive oil; IR (neat), 1635 cm-1 (C=C--N). This compound was prepared Into a dry, nitrogen filled one liter 3-neck flask fitted with reflux condenser serum cap to maintain gentle reflux was added to the warm reaction mixture at a rate sufficient to maintain gentle refluxing The reaction mixture was cooled in an ice-bath The organic layer was separated the aqueous phase was extracted with ether The combined extracts were washed with water (2×100 ml) dried (MgSO4) Removal of the solvent by evaporation

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

実験手順: To a stirred mixture of 3,4-Dichloro-phenylacetonitrile (4.65 g. 25 mmol) triethylbenzylammonium chloride (0.2 g) and 1-bromochoroethane (4.2 ml, 50 mmol), 50% sodium hydroxide (16 ml, 200 mmol) was added dropwise at 50° then the reaction was stirred at 50° for 10 hrs. After cooling to rt, the reaction mixture was diluted with water and extracted with EtOAc (×3). The layers were separated, washed with water (×3) and brine, then dried over MgSO4. Evaporation of the solvent under reduced pressure afforded the title compound (5.43 g) which was then recrystallized from Et2O/hexanes as a pale pink solid (4.49 g, 85%). Lc/MS(ES) m/e 212 [M+H]+. was added dropwise at 50° extracted with EtOAc (×3) The layers were separated washed with water (×3) and brine dried over MgSO4 Evaporation of the solvent under reduced pressure

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

実験手順: To a stirred mixture of 3,4-Dichloro-phenylacetonitrile (4.65 g. 25 mmol) triethylbenzylammonium chloride (0.2 g) and 1-bromochoroethane (4.2 ml, 50 mmol), 50% sodium hydroxide (16 ml, 200 mmol) was added dropwise at 50° then the reaction was stirred at 50° for 10 hrs. After cooling to rt, the reaction mixture was diluted with water and extracted with EtOAc (×3). The layers were separated, washed with water (×3) and brine, then dried over MgSO4. Evaporation of the solvent under reduced pressure afforded the title compound (5.43 g) which was then recrystallized from Et2O/hexanes as a pale pink solid (4.49 g, 85%). Lc/MS(ES) m/e 212 [M+H]+. was added dropwise at 50° extracted with EtOAc (×3) The layers were separated washed with water (×3) and brine dried over MgSO4 Evaporation of the solvent under reduced pressure

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

実験手順: This compound was prepared according to the procedure described by Evans, et al., J. Org. Chem. 35, 4122 (1970) for the synthesis of 3-methyl-1,2,4,5-tetrahydro-3H-benz[e]indole as follows. Into a dry, nitrogen filled, one liter 3-neck flask fitted with reflux condenser, serum cap, dropping funnel and magnetic stirrer, was added a solution of 38.55 g (167.9 mmol) XIIa in dry tetrahydrofuran (THF) (50 ml) which was placed under a slow stream of nitrogen. A 2.20 M solution of isopropyl magnesium chloride in THF (96.1 ml, 211.7 mmol) was added slowly via a syringe at such a rate as to maintain gently reflux. After the addition (15 min), 30.72 g (214.2 mmol) of bromochloroethan was added to the warm reaction mixture at a rate sufficient to maintain gentle refluxing. After the addition of the alkylhalide, an additional 52.3 ml (115 mmol) of the Grignard reagent was added to the reaction again at a controlled rate. The reaction mixture was cooled in an ice-bath and 270 ml of 1 M aqueous solution of ethylenediaminetetraacetic acid tetrasodium salt was added slowly (with stirring) and then 600 ml of a 1:1 etherbenzene was added. The organic layer was separated and the aqueous phase was extracted with ether. The combined extracts were washed with water (2×100 ml) and dried (MgSO4). Removal of the solvent by evaporation gave 43.0 g (99%) of XIIIa as a pale yellow oxygen-sensitive oil; IR (neat), 1635 cm-1 (C=C--N). This compound was prepared Into a dry, nitrogen filled one liter 3-neck flask fitted with reflux condenser serum cap to maintain gently reflux was added to the warm reaction mixture at a rate sufficient to maintain gentle refluxing The reaction mixture was cooled in an ice-bath 600 ml of a 1:1 etherbenzene was added The organic layer was separated the aqueous phase was extracted with ether The combined extracts were washed with water (2×100 ml) dried (MgSO4) Removal of the solvent by evaporation