dimethyl 2-hydroxybutanedioate

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

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

Procedure: To a solution of diisopropylamine (14 mL, 100 mmol) in THF at 0° C. was added n-butyllithium (2.5 M in hexane, 40 mL, 100 mmol) over 10 min. The mixture was stirred at RT for 30 min., and then added via cannula to a −78° C. solution of dimethyl malate F-1 (7.71 g, 47.6 mmol) in THF (130 mL). The mixture was warmed to −20° C. over 2 h, and then cooled to −78° C. Crotyl bromide (8.1 g, 60 mmol) was added, then the mixture was allowed to warm to room temperature and then stirred overnight. The solution was then cooled to −10° C. and quenched with NH4Cl (10%, 100 mL). The THF was removed and the residue extracted with ethyl acetate (2×200 mL). The combined organic layers were washed with HCl (1N, 3×50 mL), saturated aqueous sodium bicarbonate (3×50 mL), and brine, then dried over Na2SO4. The solution was filtered and concentrated to give a residue, which was purified on silica gel (ethyl acetate/hexane 1:4) to afford (2S,3R)-3-(2-butenyl)-2-hydroxysuccinic dimethyl ester F-2 (2.5 g, 24%). The mixture was warmed to −20° C. over 2 h cooled to −78° C to warm to room temperature stirred overnight The solution was then cooled to −10° C. quenched with NH4Cl (10%, 100 mL) The THF was removed the residue extracted with ethyl acetate (2×200 mL) The combined organic layers were washed with HCl (1N, 3×50 mL), saturated aqueous sodium bicarbonate (3×50 mL), and brine dried over Na2SO4 The solution was filtered concentrated to give a residue, which was purified on silica gel (ethyl acetate/hexane 1:4)

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

Procedure: [Ru(CH3CN)3(triphos)](CF3SO3)2 (11.5 mg), dimethyl DL-malate (0.65 g), and 1.0 ml of methanol were added into a 20-ml Schlenk tube under an argon atmosphere, and the mixture was stirred for 5 minutes at room temperature. This liquid was transferred to a 100-ml autoclave having a stirrer placed inside, under an argon atmosphere. The autoclave was purged with hydrogen, and then hydrogen was further included in the autoclave up to 4.0 MPa. The contents of the autoclave were heated and stirred at 100° C. for 14 hours. After cooling, the reaction liquid was analyzed by gas chromatography, and it was found that 1,2,4-butanetriol was produced at a yield of 30.6%, β-hydroxy-γ-butyrolactone at a yield of 42.3%, and methyl 3,4-dihydroxybutanoate at a yield of 21.4%. The autoclave was purged with hydrogen The contents of the autoclave were heated stirred at 100° C. for 14 hours After cooling the reaction liquid

Conditions: temp:115.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A 100 mL three-neck flask, equipped with a magnetic stir bar, a Claisen adapter with a thermocouple and a nitrogen inlet, and a short path condenser, was charged with 4.45 grams of dimethyl malate, 40 mL 1-butanol, and 0.51 gram of p-toluenesulfonic acid. The reaction was stirred at 115° C. for 3.7 hours with a nitrogen sweep. The reaction mixture was taken up in ethyl acetate, extracted with dilute aqueous sodium bicarbonate, washed three times with water, dried over magnesium sulfate, and filtered. Solvent was removed by rotary evaporation to yield 6.8 grams of a straw-colored liquid. A 100 mL three-neck flask, equipped with a magnetic stir bar extracted with dilute aqueous sodium bicarbonate washed three times with water dried over magnesium sulfate filtered Solvent was removed by rotary evaporation

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

Procedure: 46.4 g (0.2 mol) of silver oxide were added in portions, with constant stirring, to a mixture of 16.2 g (0.1 mol) of malic acid dimethyl ester and 57 g (0.30 mol) of 2-fluorobenzyl bromide. An exothermic reaction started slowly, and the temperature rose to 80° C. After cooling, 200 ml of ether were added, the solid was filtered off, the filtrate was concentrated and the residue was distilled at 180° C. in a waterpump vacuum. 19.6 g (72.6% of theory) of 2-(2-fluorobenzyloxy)-butane-1,4-dicarboxylic acid dimethyl ester were obtained. An exothermic reaction rose to 80° C After cooling the solid was filtered off the filtrate was concentrated the residue was distilled at 180° C. in a waterpump vacuum

Conditions: temp:0.00; pressure:0.00; stir:

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

Procedure: The process of claim 18 wherein about one equivalent of the lithium borohydride is reacted with the hydroxy butane dioic acid dimethyl ester to produce the 3,4-dihydroxybutyric acid -1-methyl ester.