1: With piperidine; hydrogenchloride in di-isopropyl ether; water T=40 - 55°C; P=760.051 Torr; Heating / reflux; 2: With water; sodium hydroxide in methanol 3 h; Heating / reflux; 3: With hydrogenchloride in methanol; water T=35 - 40°C; pH=5.0 - 5.2;

potassium hydroxide in ethanol

1: 91 percent / K2CO3 / dimethylformamide / 17 h / 80 °C 2: 96 percent / H2, NaOAc / 10percent Pd/C / methanol / 18 h 3: 1.) LDA / 1.) THF, hexane, -78 deg C, 30 min, 2.) THF, 30 min 4: DMAP / CH2Cl2 / 2 h / Ambient temperature 5: DBU / toluene / 3 h / 80 °C 6: 58 percent / 3.75 M aq. NaOH / aq. ethanol / 4 h View Scheme

1: K2CO3 / dimethylformamide / 1 h / 70 °C 2: 1.) H2, KOAc, 2.) MnO2 / 1.) 10percent Pd/C / 1.) MeOH, 40 psi, 1.25 h, 2.) CH2Cl2, reflux 3: 1.) LDA / 1.) THF, hexane, -78 deg C, 60 min, 2.) THF, hexane, -78 deg C, 10 min 4: (dimethylamino)pyridine / CH2Cl2 / 19 h 5: DBU / toluene / 1 h / 100 °C 6: 70 percent / 10percent aq. NaOH / ethanol / 17 h / Ambient temperature View Scheme

1: 1.) H2, KOAc, 2.) MnO2 / 1.) 10percent Pd/C / 1.) MeOH, 40 psi, 1.25 h, 2.) CH2Cl2, reflux 2: 1.) LDA / 1.) THF, hexane, -78 deg C, 60 min, 2.) THF, hexane, -78 deg C, 10 min 3: (dimethylamino)pyridine / CH2Cl2 / 19 h 4: DBU / toluene / 1 h / 100 °C 5: 70 percent / 10percent aq. NaOH / ethanol / 17 h / Ambient temperature View Scheme

1: With water; sodium hydroxide in ethanol 5 h; 2: With hydrogenchloride in ethanol; water T=60°C; pH=5; Product distribution / selectivity;

1: 1.) LDA / 1.) THF, hexane, -78 deg C, 30 min, 2.) THF, 30 min 2: DMAP / CH2Cl2 / 2 h / Ambient temperature 3: DBU / toluene / 3 h / 80 °C 4: 58 percent / 3.75 M aq. NaOH / aq. ethanol / 4 h View Scheme

sodium hydroxide in water T=25 - 30°C; pH=7.0 - 7.25; Product distribution / selectivity;

potassium hydroxide; 1,8-diazabicyclo[5.4.0]undec-7-ene 1.) toluene, 2.) EtOH; Yield given. Multistep reaction;

1: DMAP / CH2Cl2 / 2 h / Ambient temperature 2: DBU / toluene / 3 h / 80 °C 3: 58 percent / 3.75 M aq. NaOH / aq. ethanol / 4 h View Scheme