1: trans-5-chloro-2,3,3a,12b-tetrahydro-1H-dibenzo[2,3:6,7]oxepino[4,5-c]pyrrole hydrochloride With sodium hydroxide in dichloromethane; water pH=> 10; 2: formaldehyd With formic acid in water; toluene T=60°C; 2 h; 3: cis-maleic acid

in ethanol; tert-butyl methyl ether T=0 - 20°C; 2 h; SolventTemperatureTime;

1: asenapine phosphate With sodium hydrogencarbonate in toluene T=25°C; 0.5 h; Industry scale; 2: cis-maleic acid in isopropyl alcohol T=25 - 50°C; Industry scale;

1.1: potassium carbonate; copper / o-xylene / 25 - 30 °C / Reflux 2.1: thionyl chloride / N,N-dimethyl-formamide; toluene / 40 - 50 °C 2.2: 0 - 30 °C 3.1: potassium tert-butylate / toluene / 15 - 30 °C / Inert atmosphere 3.2: 0 - 5 °C / pH 2 - 2.5 4.1: phosphorus pentoxide; phosphoric acid / 100 - 120 °C 5.1: magnesium / methanol / 25 - 65 °C / Reflux 6.1: lithium aluminium tetrahydride; AlCl3, aluminium chloride / tetrahydrofuran / -5 - 5 °C 6.2: -5 - 5 °C 7.1: isopropyl alcohol / 60 °C View Scheme

1.1: caesium carbonate / copper(l) chloride; N,N-dimethylaminoacetic acid / 1,4-dioxane / 110 - 115 °C 1.2: 5 h / 25 - 65 °C 2.1: hydrogenchloride / dichloromethane; water / pH 1.5 2.2: 0.75 h / 0 - 15 °C 3.1: potassium tert-butylate / toluene / 3 h / 20 °C 3.2: 3 h / 20 °C 4.1: phosphorous pentoxide; phosphoric acid / 96 h / 115 - 120 °C 5.1: formic acid; iodine; magnesium / toluene; methanol / 5 h / 20 - 40 °C 5.2: 5 - 10 °C / pH ~ 1 6.1: sodium tetrahydroborate / tetrahydrofuran / 0.25 h / 20 °C 6.2: 6 h / Reflux 6.3: 10 - 15 °C 7.1: isopropyl alcohol / 13.75 h / -10 - 65 °C View Scheme

1.1: magnesium / methanol / 25 - 65 °C / Reflux 2.1: lithium aluminium tetrahydride; AlCl3, aluminium chloride / tetrahydrofuran / -5 - 5 °C 2.2: -5 - 5 °C 3.1: isopropyl alcohol / 60 °C View Scheme

1.1: potassium carbonate / copper / 10 h / 130 °C 2.1: morpholine; sulfur / 12 h / 110 °C 2.2: 8 h / Reflux 3.1: sulfuric acid / 2 h / 50 °C 4.1: sodium t-butanolate / tert-butyl methyl ether / 2 h / 5 - 20 °C 5.1: (S)-pyrophosphoric acid / water / 2 h / 0 - 60 °C 6.1: 1,8-diazabicyclo[5.4.0]undec-7-ene / 20 - 35 °C 7.1: hydrogen / Ni-Raney / tetrahydrofuran / 48 h / 20 °C / 2585.81 - 3102.97 Torr 8.1: ethyl acetate / 96 h / 25 °C 9.1: boron trifluoride diethyl etherate; triethylsilane / 24 h / 105 °C 10.1: sodium hydroxide / dichloromethane; water / pH > 10 10.2: 2 h / 60 °C View Scheme

1.1: potassium carbonate / copper / 10 h / 130 °C 2.1: morpholine; sulfur / 12 h / 110 °C 2.2: 8 h / Reflux 3.1: sulfuric acid / 2 h / 50 °C 4.1: sodium t-butanolate / tert-butyl methyl ether / 2 h / 5 - 20 °C 5.1: (S)-pyrophosphoric acid / water / 2 h / 0 - 60 °C 6.1: 1,8-diazabicyclo[5.4.0]undec-7-ene / 20 - 35 °C 7.1: hydrogen / Ni-Raney / tetrahydrofuran / 48 h / 20 °C / 2585.81 - 3102.97 Torr 8.1: ethyl acetate / 96 h / 25 °C 9.1: boron trifluoride diethyl etherate; triethylsilane / 24 h / 105 °C 10.1: sodium hydroxide / dichloromethane; water / pH > 10 10.2: 2 h / 60 °C View Scheme

1.1: (S)-pyrophosphoric acid / water / 2 h / 0 - 60 °C 2.1: 1,8-diazabicyclo[5.4.0]undec-7-ene / 20 - 35 °C 3.1: hydrogen / Ni-Raney / tetrahydrofuran / 48 h / 20 °C / 2585.81 - 3102.97 Torr 4.1: ethyl acetate / 96 h / 25 °C 5.1: boron trifluoride diethyl etherate; triethylsilane / 24 h / 105 °C 6.1: sodium hydroxide / dichloromethane; water / pH > 10 6.2: 2 h / 60 °C View Scheme

1.1: sodium t-butanolate / tert-butyl methyl ether / 2 h / 5 - 20 °C 2.1: (S)-pyrophosphoric acid / water / 2 h / 0 - 60 °C 3.1: 1,8-diazabicyclo[5.4.0]undec-7-ene / 20 - 35 °C 4.1: hydrogen / Ni-Raney / tetrahydrofuran / 48 h / 20 °C / 2585.81 - 3102.97 Torr 5.1: ethyl acetate / 96 h / 25 °C 6.1: boron trifluoride diethyl etherate; triethylsilane / 24 h / 105 °C 7.1: sodium hydroxide / dichloromethane; water / pH > 10 7.2: 2 h / 60 °C View Scheme