1: tetrahydrofuran; diethyl ether / 3 h / 20 °C 2: lithium aluminium tetrahydride / diethyl ether / 2 h / Reflux 3: phosphoric acid / 3 h 4: N,N-dimethyl-formamide / 4 h / Reflux View Scheme

in N,N-dimethyl-formamide 4 h; Reflux;

1: With sodium hydride in dimethyl sulfoxide T=25°C; 2.67 h; 2: With hydrogen bromide in water T=10°C; pH=7;

1: 1-(4'-fluorophenyl)-1,3-dihydroisobenzofuran-5-carbonitrile; 1-dimethylamino-3-chloropropane With sodium hydride in dimethyl sulfoxide; toluene T=20 - 25°C; 2.75 - 3.83333 h; 2: 1-[3-(dimethylamino)propyl]-1-(4-fluorophenyl)-1,3-dihydro-5-isobenzofuran-carbonitrile With hydrogen bromide in water; isopropyl alcohol; toluene pH=8 - 8.5; 13 h;

1: sodium hydride in paraffin oil (nujol); dimethyl sulfoxide T=60 - 65°C; Heating / reflux; 2: 1-(4'-fluorophenyl)-1,3-dihydroisobenzofuran-5-carbonitrile; 1-dimethylamino-3-chloropropane With sodium methylsulfinylmethanide in water; dimethyl sulfoxide; toluene T=25 - 30°C; 2.75 - 3.83333 h; 3: 1-[3-(dimethylamino)propyl]-1-(4-fluorophenyl)-1,3-dihydro-5-isobenzofuran-carbonitrile With hydrogen bromide in water; isopropyl alcohol; toluene pH=8.5 - 9; 11 h;

1: With sodium hydride in 1,3-dimethyl-imidazolidin-2-one; toluene T=40 - 50°C; 0.666667 h; 2: With hydrogenchloride; water T=65 - 70°C; 3 h; 3: With sodium hydroxide in water; toluene Product distribution / selectivity;

N,N,N',N,-tetramethylethylenediamine in tetrahydrofuran; tert-butyl methyl ether; N,N-dimethyl-formamide

N,N,N',N,-tetramethylethylenediamine in N,N-dimethyl-formamide; toluene

1: 1-Amino-3-chloro-propane hydrochloride With sodium hydroxide in water; toluene 0.166667 - 0.25 h; 2: 1-(4'-fluorophenyl)-1,3-dihydroisobenzofuran-5-carbonitrile With potassium tert-butylate in dimethyl sulfoxide; toluene T=40 - 45°C; 1 h;

1.1: sodium methylsulfinylmethide / dimethylsulfoxide; various solvent(s) / 0.33 h 1.2: dimethylsulfoxide; various solvent(s) / 1 h / 20 °C 2.1: 4.11 g / aq. HCl View Scheme