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With sodium methylate; In methanol; diethyl ether; ethyl acetate; |
b) Preparation of (2R,5R)-2,5-hexanediol A 1000 mL jacketed reaction vessel is charged with (3R)-3-hydroxybutyric acid (52.0 g, 0.5 mol), methanol (390 mL) and sodium methoxide (110 mL of a 0.5N solution in methanol, 0.055 mol), and the mixture (pH=5.38) was cooled to 0 C. with a circulating bath. The electrode configuration used consists of a Pt foil anode (20 cm2) wrapped around the outside bottom of a small jointed tube which fits inside a larger jointed tube with a Pt foil cathode (30 cm2) lining the inside (avg electrode gap=2.5 mm). Using a 30 amp DC power supply (Hewlett Packard Model No. 6269B), a constant current (current density 0.25 A/cm2) of 5 amp was applied until 56,000 coulombs (1.2 F/mol) were passed at which point complete conversion of hydroxy acid was indicated by gas chromatography. The reaction and gas evolution (H2 and CO2) proceed normally until ca. 1.0 F/mol current are passed, after which the resistance and solution pH are observed to increase. The colorless reaction mixture was then concentrated on a rotovap, and the resulting solid residue was extracted EtOAc (500 mL). After filtering, the remaining solids were stirred with EtOAc (100 mL) for 10 h, filtered, and the combined EtOAc extracts (600 mL) were concentrated to a colorless solid. The solids were dissolved in a minimum amount of warm Et2 O, quickly filtered through a coarse frit, and the filtrate cooled to -78 C. After two hours, the colorless crystals were filtered, washed with cold pentane, and dried in vacuo (Yield 14.4 g, 48%). mp 53-54 C.; [alpha]25 D=-39.6+-0.5 (c 1, CHCl3) 1 H NMR (CD2 Cl2) delta 1.15 (d, JHH =6.2 Hz, 6H, CH3), 1.50 (m, 4H, CH2), 2.95 (br, 2H, OH), 3.75 (m, 2H, CH); 13 C NMR (CD2 Cl2) delta 23.6, 35.9, 68.1. Anal. Calcd for C6 H14 O2: C, 60.98; H, 11.94. Found: C, 61.12; H, 11.64. |
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With sodium methylate; In methanol; diethyl ether; ethyl acetate; |
c) (2R,5R)-2,5-hexanediol A 1000 mL jacketed reaction vessel was charged with (3R)-3-hydroxybutyric acid (52.0 g, 0.5 mol), methanol (390 mL) and sodium methoxide (110 mL of a 0.5 N solution in methanol, 0.055 mol), and the mixture (pH=5.38) was cooled to 0 C. with a circulating bath. The electrode configuration used consists of a Pt foil anode (20 cm2) wrapped around the outside bottom of a small jointed tube which fit inside a larger jointed tube with a Pt foil cathode (30 cm2) lining the inside (avg electrode gap=2.5 mm). Using a 30 amp DC power supply (Hewlett Packard Model No. 6269B), a constant current (current density 0.25 A/cm2) of 5 amp was applied until 56,000 coulombs (1.2 F/mol) were passed at which point complete conversion of hydroxy acid was indicated by gas chromatography. The reaction and gas evolution (H2 and CO2) proceed normally until ca. 1.0 F/mol current were passed, after which the resistance and solution pH are observed to increase. The colorless reaction mixture was then concentrated on a rotovap, and the resulting solid residue was extracted EtOAc (500 mL). After filtering, the remaining solids were stirred with EtOAc (100 mL) for 10 h, filtered, and the combined EtOAc extracts (600 mL) were concentrated to a colorless solid. The solids were dissolved in a minimum amount of warm Et2 O, quickly filtered through a coarse frit, and the filtrate cooled to -78 C. After two hours, the colorless crystals were filtered, washed with cold pentane, and dried in vacuo (Yield 14.4 g, 48%). mp 53-54 C.; [alpha]25 =-39.6+-0.50 (c 1, CHCl3) 1 H NMR (CD2 Cl2) delta 1.15 (d, JHH =6.2 Hz, 6H, CH3), 1.50 (m, 4H, CH2), 2.95 (br, 2H, OH), 3.75 (m, 2H, CH); 13 C NMR (CD2 Cl2) d 23.6, 35.9, 68.1. Anal. Calcd for C6 H14 O2: C, 60.98; H, 11.94. Found: C, 61.12; H, 11.64. |
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