3,3-dimethyl-1,4-dihydroquinoxalin-2-one

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

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

Procedure: 5.4 parts of o-phenylenediamine and 40 parts chloroform are placed in a 250 ml flask, 20 parts 50% by weight NaOH solution is added followed by 0.5 part benzyl triethyl ammonium chloride (BTAC). The flask is cooled in an ice-bath and 5.5 parts acetone cyanohydrin in 10 parts chloroform are added dropwise over 30 minutes. The flask is cooled in the ice-bath for an additional two hours, then warmed and maintained at room temperature for another two hours. Conversion in excess of 90% is obtained. The reaction product is worked up, filtered and washed with CHCl3 several times, and dried to yield 3,3-dimethyl-1,2,3,4-tetrahydroquinoxalin-2-one, which is dissolved in ethanol and conventionally hydrogenated. The flask is cooled in an ice-bath warmed Conversion in excess of 90% is obtained filtered washed with CHCl3 several times dried

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

Procedure: In a 200-mL r.b. flask, a solution of 3,4-dihydro-3,3-dimethylquinoxalin-2(1H)-one (1.00 g, 5.66 mmol) in dry THF was treated with NaH (0.28 g, 7.09 mmol, 1.25 equiv). The reaction mixture was stirred at room temperature for 30 minutes before iodomethane (0.39 mL, 6.24 mmol, 1.1 equiv) was added to the reaction flask. The reaction was then stirred at room temperature overnight then partitioned between EtOAc (100 mL) and H2O (20 mL). The aqueous layer was extracted with EtOAc (2×30 mL). The combined organic layers were then washed with brine (20 mL), dried (MgSO4), filtered, and concentrated to a thick oil. Purification by flash chromatography (25% EtOAc/hexane) afforded 830 mg (78%) of 3,4-dihydro-1,3,3-trimethylquinoxalin-2(1H)-one as a white solid. Data for 3,4-dihydro-1,3,3-trimethylquinoxalin-2(1H)-one: 1H NMR (400 MHz, CDCl3) δ 6.90 (m, 3H), 6.67 (d, J=7.7, 1H), 3.69 (bs, 1H), 3.36 (s, 3H), 1.37 (s, 6H). was added to the reaction flask then partitioned between EtOAc (100 mL) and H2O (20 mL) The aqueous layer was extracted with EtOAc (2×30 mL) The combined organic layers were then washed with brine (20 mL) dried (MgSO4) filtered concentrated to a thick oil Purification by flash chromatography (25% EtOAc/hexane)

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

Procedure: In a 200-mL r.b. flask, a solution of 3,4-dihydro-3,3-dimethylquinoxalin-2(1H)-one (1.00 g, 5.66 mmol) in dry THF was treated with NaH (0.28 g, 7.09 mmol, 1.25 equiv). The reaction mixture was stirred at room temperature for 30 minutes before iodomethane (0.39 mL, 6.24 mmol, 1.1 equiv) was added to the reaction flask. The reaction was then stirred at room temperature overnight then partitioned between EtOAc (100 mL) and H2O (20 mL). The aqueous layer was extracted with EtOAc (2×30 mL). The combined organic layers were then washed with brine (20 mL), dried (MgSO4), filtered, and concentrated to a thick oil. Purification by flash chromatography (25% EtOAc/hexane) afforded 830 mg (78%) of 3,4-dihydro-1,3,3-trimethylquinoxalin-2(1H)-one as a white solid. Data for 3,4-dihydro-1,3,3-trimethylquinoxalin-2(1H)-one: 1H NMR (400 MHz, CDCl3) δ 6.90 (m, 3H), 6.67 (d, J=7.7, 1H), 3.69 (bs, 1H), 3.36 (s, 3H), 1.37 (s, 6H). was added to the reaction flask then partitioned between EtOAc (100 mL) and H2O (20 mL) The aqueous layer was extracted with EtOAc (2×30 mL) The combined organic layers were then washed with brine (20 mL) dried (MgSO4) filtered concentrated to a thick oil Purification by flash chromatography (25% EtOAc/hexane)

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

Procedure: In a manner analogous with the foregoing, 3,3-dimethyl-3,4-dihydroquinoxalin-2-one is hydrogenated at about 130° C. and 1500 psi in the presence of rhodium (5%) on charcoal in 2 hours, to yield cis-3,3-dimethyl-decahydroquinoxalin-2-one. is hydrogenated at about 130° C.

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

Procedure: In a manner analogous with the foregoing, 3,3-dimethyl-3,4-dihydroquinoxalin-2-one is hydrogenated at about 130° C. and 1500 psi in the presence of rhodium (5%) on charcoal in 2 hours, to yield cis-3,3-dimethyl-decahydroquinoxalin-2-one. is hydrogenated at about 130° C.

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

Procedure: In a manner analogous with the foregoing, 3,3-dimethyl-3,4-dihydroquinoxalin-2-one is hydrogenated at about 130° C. and 1500 psi in the presence of rhodium (5%) on charcoal in 2 hours, to yield cis-3,3-dimethyl-decahydroquinoxalin-2-one. is hydrogenated at about 130° C.

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

Procedure: 5.4 parts of o-phenylenediamine and 40 parts chloroform are placed in a 250 ml flask, 20 parts 50% by weight NaOH solution is added followed by 0.5 part benzyl triethyl ammonium chloride (BTAC). The flask is cooled in an ice-bath and 5.5 parts acetone cyanohydrin in 10 parts chloroform are added dropwise over 30 minutes. The flask is cooled in the ice-bath for an additional two hours, then warmed and maintained at room temperature for another two hours. Conversion in excess of 90% is obtained. The reaction product is worked up, filtered and washed with CHCl3 several times, and dried to yield 3,3-dimethyl-1,2,3,4-tetrahydroquinoxalin-2-one, which is dissolved in ethanol and conventionally hydrogenated. The flask is cooled in an ice-bath warmed Conversion in excess of 90% is obtained filtered washed with CHCl3 several times dried

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

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

Procedure: To a solution of 1,2-phenylenediamine (16.96 g) in N,N-dimethylformamide (80 mL) were added successively N,N-diisopropylethylamine (36.4 mL) and ethyl α-bromoisobutyrate (39.8 g), and the mixture was heated at 110° C. for 3 days. After cooling, to the reaction mixture was added cold water and the mixture was extracted with ethyl acetate. The aqueous layer was extracted with ethyl acetate, and the combined organic layer was washed successively with an aqueous 10% HCl solution, water, an aqueous saturated sodium hydrogencarbonate solution and brine, dried over sodium sulfate and concentrated in vacuo. The resultant residue was recrystallized from dichloromethane-n-hexane to give 3,3-dimethyl-3,4-dihydroquinoxalin-2(1H)-one (15.90 g) as pale yellow crystals. After cooling, to the reaction mixture the mixture was extracted with ethyl acetate The aqueous layer was extracted with ethyl acetate the combined organic layer was washed successively with an aqueous 10% HCl solution, water an aqueous saturated sodium hydrogencarbonate solution and brine, dried over sodium sulfate concentrated in vacuo The resultant residue was recrystallized from dichloromethane-n-hexane