decane-4,7-dione

Conditions: temp:-15.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The title compound was prepared from cis-1-benzyl-2,5-dipropylpyrrolidine. Dissolve 11.92 grams of decane-4,7-dione in 4.62 grams acetic acid and 100 mL methanol. Add 1.16 grams potassium hydroxide pellets. Stir to dissolve the potassium hydroxide. Cool the reaction mixture in an ice acetone bath at −15° C. Add 7.50 grams benzylamine followed immediately with 5.4 grams sodium cyanoborohydride in several portions. Let the reaction mixture warm up to room temperature over two days. Add 45 mL 4 N HCl drop-wise and stir for 30 minutes. Evaporate the reaction mixture under reduced pressure to remove most of the solvents. Dilute the residue with water, filter off some white solid, and extract the aqueous layer with ether. This ether solution contained 2,5-dipropylpyrrole. Cool the aqueous layer with an ice bath and add solid sodium hydroxide in small portions with stirring until pH-13. Dissolve the white solid above in this mixture. Extract with ether several times. Wash the combined ether solution with saturated brine, dry over anhydrous Na2SO4 and evaporate to give the crude 1-benzyl-2,5-dipropylpyrrolidine. The cis and trans isomers were separated on silica gel (5-10% EtOAc in hexanes with 1% Et3N). The slow eluting isomer was cis-1-benzyl-2,5-dipropylpyrrolidine. 1H NMR (CDCl3, 500 MHz) δ7.29-7.35 (m, 4H), 7.24-7.26 (m, 1H), 3.77 (s, 2H), 2.53-2.58 (m, 2H), 1.77-1.84 (m, 2H), 1.52-1.58 (m, 2H), 1.27-1.44 (m, 4H), 1.13-1.25 (m, 4H), 0.865 (t, J=7.2 Hz, 61). warm up to room temperature over two days stir for 30 minutes Evaporate the reaction mixture under reduced pressure to remove most of the solvents Dilute the residue with water filter off some white solid extract the aqueous layer with ether Cool the aqueous layer with an ice bath add solid sodium hydroxide in small portions with stirring until pH-13 Dissolve the white solid above in this mixture Extract with ether several times Wash the combined ether solution with saturated brine dry over anhydrous Na2SO4 evaporate

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

Procedure: Cool a suspension of 20.42 g N,N′-dimethoxy-N,N′-dimethylsuccinamide from the Step A above in 1 L anhydrous ether in an ice bath under nitrogen. Add 300 mL of 2 M propylmagnesium chloride in ether over 15 minutes with mechanical stir. Continue to stir the reaction mixture in the cooling bath for 2.25 hours. Quench the reaction by adding 30 mL ethanol in 50 mL ether over 30 minutes. Pour the resulting suspension into 1 L ice and water containing 75 mL concentrated HCl. Separate the layers, wash the organic layer with dilute HCl, 5% NaHCO3 and saturated brine. Dry over anhydrous Na2SO4. Evaporate the clear yellowish solution to give the title compound as yellow solid. 1H NMR (CDCl3, 500 MHz) δ: 2.69 (s, 4H), 2.46 (t, J=7.4 Hz, 411), 1.60-1.67 (m, 4H), 0.935 (t, J=7.5 Hz, 61). Cool Quench the reaction Separate the layers wash the organic layer with dilute HCl, 5% NaHCO3 and saturated brine Dry over anhydrous Na2SO4 Evaporate the clear yellowish solution

Conditions: temp:-15.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Dissolve 11.92 g decane-4,7-dione from the Step B above in 4.62 g acetic acid and 100 mL methanol. Add 1.16 g potassium hydroxide pellets. Stir to dissolve the potassium hydroxide. Cool the reaction mixture in an ice acetone bath at −15° C. Add 7.50 g benzylamine followed immediately with 5.4 g sodium cyanoborohydride in several portions. Let the reaction mixture warm up to room temperature over two days. Add 45 mL 4 N HCl drop-wise and stir for 30 minutes. Evaporate the reaction mixture under reduced pressure to remove most of the solvents. Dilute the residue with water, filter off some white solid, and extract the aqueous layer with ether. This ether solution contained 2,5-dipropylpyrrole. Cool the aqueous layer with an ice bath and add solid sodium hydroxide in small portions with stir until pH ˜13. Dissolve the white solid above in this mixture. Extract with ether several times. Wash the combined ether solution with saturated brine, dry over anhydrous Na2SO4 and evaporate to give the crude 1-benzyl-2,5-dipropylpyrrolidine. The cis and trans isomers were separated on silica gel (5˜10% EtOAc in hexanes with 1% Et3N). The fast eluting isomer was trans-1-benzyl-2,5-dipropylpyrrolidine. 1H NMR (CDCl3, 500 MHz) δ 7.38 (d, J=7.6 Hz, 2H), 7.29˜7.33 (m, 2H), 7.21˜7.24 (m, 1H), 3.83 (d, J=13.9 Hz, 1H), 3.66 (d, J=14.0 Hz, 1H), 2.86 (br s, 2H), 1.85˜1.94 (m, 2H), 1.45˜1.60 (m, 4H), 1.27˜1.37 (m, 2H), 1.09˜1.20 (m, 4H), 0.875 (t, J=7.2 Hz, 6H). The slower-eluting isomer was cis-1-benzyl-2,5-dipropylpyrrolidine. 1H NMR (CDCl3, 500 MHz) 7.29˜7.35 (m, 4H), 7.24˜7.26 (m, 1H), 3.77 (s, 2H), 2.53˜2.58 (m, 2H), 1.77˜1.84 (m, 2H), 1.52˜1.58 (m, 2H), 1.27˜1.44 (m, 4H), 1.13˜1.25 (m, 4H), 0.865 (t, J=7.2 Hz, 6H). warm up to room temperature over two days stir for 30 minutes Evaporate the reaction mixture under reduced pressure to remove most of the solvents Dilute the residue with water filter off some white solid extract the aqueous layer with ether Cool the aqueous layer with an ice bath add solid sodium hydroxide in small portions with stir until pH ˜13 Dissolve the white solid above in this mixture Extract with ether several times Wash the combined ether solution with saturated brine dry over anhydrous Na2SO4 evaporate

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

Procedure: Cool a suspension of 20.42 g N,N′-dimethoxy-N,N′-dimethylsuccinamide from the Step A above in 1 L anhydrous ether in an ice bath under nitrogen. Add 300 mL of 2 M propylmagnesium chloride in ether over 15 minutes with mechanical stir. Continue to stir the reaction mixture in the cooling bath for 2.25 hours. Quench the reaction by adding 30 mL ethanol in 50 mL ether over 30 minutes. Pour the resulting suspension into 1 L ice and water containing 75 mL concentrated HCl. Separate the layers, wash the organic layer with dilute HCl, 5% NaHCO3 and saturated brine. Dry over anhydrous Na2SO4. Evaporate the clear yellowish solution to give the title compound as yellow solid. 1H NMR (CDCl3, 500 MHz) : 2.69 (s, 4H), 2.46 (t, J=7.4 Hz, 4H), 1.60˜1.67 (m, 4H), 0.935 (t, J=7.5 Hz, 6H). Cool Quench the reaction Separate the layers wash the organic layer with dilute HCl, 5% NaHCO3 and saturated brine Dry over anhydrous Na2SO4 Evaporate the clear yellowish solution

Conditions: temp:-15.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The title compound was prepared from cis-1-benzyl-2,5-dipropylpyrrolidine. Dissolve 11.92 grams of decane-4,7-dione in 4.62 grams acetic acid and 100 mL methanol. Add 1.16 grams potassium hydroxide pellets. Stir to dissolve the potassium hydroxide. Cool the reaction mixture in an ice acetone bath at −15° C. Add 7.50 grams benzylamine followed immediately with 5.4 grams sodium cyanoborohydride in several portions. Let the reaction mixture warm up to room temperature over two days. Add 45 mL 4 N HCl drop-wise and stir for 30 minutes. Evaporate the reaction mixture under reduced pressure to remove most of the solvents. Dilute the residue with water, filter off some white solid, and extract the aqueous layer with ether. This ether solution contained 2,5-dipropylpyrrole. Cool the aqueous layer with an ice bath and add solid sodium hydroxide in small portions with stirring until pH-13. Dissolve the white solid above in this mixture. Extract with ether several times. Wash the combined ether solution with saturated brine, dry over anhydrous Na2SO4 and evaporate to give the crude 1-benzyl-2,5-dipropylpyrrolidine. The cis and trans isomers were separated on silica gel (5-10% EtOAc in hexanes with 1% Et3N). The slow eluting isomer was cis-1-benzyl-2,5-dipropylpyrrolidine. 1H NMR (CDCl3, 500 MHz) δ7.29-7.35 (m, 4H), 7.24-7.26 (m, 1H), 3.77 (s, 2H), 2.53-2.58 (m, 2H), 1.77-1.84 (m, 2H), 1.52-1.58 (m, 2H), 1.27-1.44 (m, 4H), 1.13-1.25 (m, 4H), 0.865 (t, J=7.2 Hz, 61). warm up to room temperature over two days stir for 30 minutes Evaporate the reaction mixture under reduced pressure to remove most of the solvents Dilute the residue with water filter off some white solid extract the aqueous layer with ether Cool the aqueous layer with an ice bath add solid sodium hydroxide in small portions with stirring until pH-13 Dissolve the white solid above in this mixture Extract with ether several times Wash the combined ether solution with saturated brine dry over anhydrous Na2SO4 evaporate

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

Procedure: Cool a suspension of 20.42 g N,N′-dimethoxy-N,N′-dimethylsuccinamide from the Step A above in 1 L anhydrous ether in an ice bath under nitrogen. Add 300 mL of 2 M propylmagnesium chloride in ether over 15 minutes with mechanical stir. Continue to stir the reaction mixture in the cooling bath for 2.25 hours. Quench the reaction by adding 30 mL ethanol in 50 mL ether over 30 minutes. Pour the resulting suspension into 1 L ice and water containing 75 mL concentrated HCl. Separate the layers, wash the organic layer with dilute HCl, 5% NaHCO3 and saturated brine. Dry over anhydrous Na2SO4. Evaporate the clear yellowish solution to give the title compound as yellow solid. 1H NMR (CDCl3, 500 MHz) δ: 2.69 (s, 4H), 2.46 (t, J=7.4 Hz, 411), 1.60-1.67 (m, 4H), 0.935 (t, J=7.5 Hz, 61). Cool Quench the reaction Separate the layers wash the organic layer with dilute HCl, 5% NaHCO3 and saturated brine Dry over anhydrous Na2SO4 Evaporate the clear yellowish solution