Methyl -3-hydroxybutanoate

Fig. 11 Side products in the sucrose-to-lactate (green) convta ion in MeOH and their raigin blue retro-aldol of glucose (see Sect. 7) red methanolysis of sucrose ot acetalizatirai of glucose black dehydration of sugars to HMF, furan ethers and humins. MMHB methyl methoxy-2-hydroxybutanoate, MVG methyl vinyl glycolate, MHB methyl-2-hydroxybutanoate, GADMA glycolaldehyde dimethyl acetal. HG = hydrogenation...

The enantiomeric excess (ee) of the hydrogenated products was determined either by polarimetry, GLC equipped with a chiral column or H-NMR with a chiral shift reagent. Methyl lactate and methyl 3-hydroxybutanoate, obtained from 1 and 2, respectively, were analized polarimetry using a Perkin-Elmer 243B instrument. The reference values of [a]o(neat) were +8.4° for (R)-methyl pyruvate and -22.95° for methyl 3-hydroxybutcinoate. Before GLC analysis, i-butyl 5-hydroxyhexanoate, methyl 5-hydroxyhexanoate, and n-butyl 5-hydroxyhexanoate, obtained from 1, 5, and 6, respectively, were converted to the pentanoyl esters, methyl 3-hydroxybutanoate was converted to the acetyl ester, and methyl 4-methyl-3-hydroxybutanoate obtained from 2 was converted the ester of (+)-a-methyl-a-(trifluoromethyl)phenyl acetic acid (MTPA). 

Gas chromatographic analysis indicates that the yield of methyl 3-hydroxybutanoate is 98% column, PEG-20M on Chromosorb WAW (Stainless steel 3 m x 31, Gasukuro Kogyo) column temperature, 120°C injector temperature, 160°C, carrier nitrogen pressure, 1.2 kg/cm tn of methyl 3-oxobutanoate, methyl 3,3-dimethoxybutanoate, and methyl 3-hydroxybutanoate are 31.5, 34.0 and 41.7 min, respectively. 

This crude product is distilled under reduced pressure to give 48 g (70%) of pure (R)-(-)-methyl 3-hydroxybutanoate (bp 61-62°/18 mm) with a specific rotation of [a] -47.6° (CHCI3, c1.0) (Note 2). 

Drying in an evacuated desiccator over P2O5 removes water as well as methyl (R)-3-hydroxybutanoate and crotonic acid. 

ASYMMETRIC HYDROGENATION OF 3-OXO CARBOXYLATES USING BINAP-RUTHENIUM COMPLEXES (R)-(-)-METHYL 3-HYDROXYBUTANOATE (Butanoic acid, 3-hydroxy-, methyl ester, (R)-)... 

R)-(-)-Methyl 3-hydroxybutanoate Butyric acid, 3-hydroxy-, methyl ester, D-(-)-(8) Butanoic acid, 3-hydroxy- methyl ester, (R)- (9) (3976-69-0) [(R)-2,2 -Bls(dlphenylphosphino)-1,1 -binaphthyl]dichlororuthenium Ruthenium, [[1,1 -binaphthalene]-2,2 -diylbis(diphenylphosphine)-P,P ]dichloro- (12) (115245-70-0)... 

A, (R)-(-)-Methyl 3-hydroxybutanoate. A 2-L, round-bottomed flask is charged with 50 g (0.58 mol) of poly-[(R)-3-hydroxybutyric acid] (PHB) (Note 1) and 500 mL of absolute 1,2-dichloroethane. The flask is equipped with a reflux condenser, and the mixture is heated at reflux lor 1 hr. A solution of 10 mL of coned sulfuric acid in 200 mL of absolute methanol is added and the reaction mixture is heated at reflux for 3 days. During this time the mixture becomes homogeneous. 

Optically active 3-hydroxybutanoic acid and its methyl ester were first prepared by McKenzie, Magnus-Levy, and Emil Fischer.3 The biopolymer PHB and mixed polymers containing (R)-3-hydroxybutanoate and (R)-3-hydroxypentanoate were also discovered long ago,4 5 and are now produced on an industrial scale. .7 As described here, depolymerization by transesterification [H+ or Ti(OR)4 catalysis], or by hydrolysis, produces8-9 the corresponding monomeric (R)-esters and (R)-acids 1. The 3-hydroxybutanoic acid can also be prepared by hydrolysis of the ester.2-10... 

Annual Volume 71 contains 30 checked and edited experimental procedures that illustrate important new synthetic methods or describe the preparation of particularly useful chemicals. This compilation begins with procedures exemplifying three important methods for preparing enantiomerically pure substances by asymmetric catalysis. The preparation of (R)-(-)-METHYL 3-HYDROXYBUTANOATE details the convenient preparation of a BINAP-ruthenium catalyst that is broadly useful for the asymmetric reduction of p-ketoesters. Catalysis of the carbonyl ene reaction by a chiral Lewis acid, in this case a binapthol-derived titanium catalyst, is illustrated in the preparation of METHYL (2R)-2-HYDROXY-4-PHENYL-4-PENTENOATE. The enantiomerically pure diamines, (1 R,2R)-(+)- AND (1S,2S)-(-)-1,2-DIPHENYL-1,2-ETHYLENEDIAMINE, are useful for a variety of asymmetric transformations hydrogenations, Michael additions, osmylations, epoxidations, allylations, aldol condensations and Diels-Alder reactions. Promotion of the Diels-Alder reaction with a diaminoalane derived from the (S,S)-diamine is demonstrated in the synthesis of (1S,endo)-3-(BICYCLO[2.2.1]HEPT-5-EN-2-YLCARBONYL)-2-OXAZOLIDINONE. 

The preparation of enantiomerically pure chemicals is also the theme of the next group of four procedures. The biopolymer polyhydroxybutyric acid, which is now produced on an industrial scale, serves as the starting material for the large scale synthesis of (R)-3-HYDROXYBUTANOIC ACID and (R)-METHYL 3-HYDROXYBUTANOATE. Esters of (-)-camphanic acid are useful derivatives for resolving and determining the enantiomeric purity of primary and secondary alcohols. An optimized preparation of (-)-(1S,4R)-CAMPHANOYL CHLORIDE is provided. The preparation of enantiomerically pure a-hydroxyketones from ethyl lactate is illustrated in the synthesis of (3HS)-[(tert)-BUTYL-DIPHENYLSILYL)OXY]-2-BUTANONE. One use of this chiral a-hydroxyketone is provided in the synthesis of (2S,3S)-3-ACETYL-8-... 

B. Methyl 2-(benzylamino)methyl-3-hydroxybutanoate. A dried, 2-L, onenecked, round-bottomed flask, equipped with a magnetic stirring bar, is charged with 68.7 g (0.53 mol) of methyl 3-hydroxy-2-methylenebutanoate and 800 mL of anhydrous methanol. After the addition of 57.7 mL (0.53 mol) of benzylamine (Note 1), the mixture is stirred at room temperature for 48 hr (Note 3). The methanol is removed under reduced pressure to leave 125.6 g (100%) of the amino ester as a clear oil, essentially pure by 1H NMR analysis (Note 4). 

Synthesis of Methyl (S)-4-Chloro-3- and Methyl (S)-4-Cyano-3-hydroxybutanoate 199... 

To a solution of methyl 4-chloro-3-hydroxybutanoate (0.50 g, 3.3 mmol) in 62 ml tris-SO4 buffer (0.5 m, pH 7.5) NaCN was added (322 mg, 6.6 mmol), followed by addition of purified HheC-W249F halohydrin dehalogenase (15 mg in 3 ml buffer). The resulting mixture was stirred at ambient temperature (22 °C) for 5 h. 

In addition, a sample of (S)-hydroxyester of 85% e.e. was converted to the optically pure (R)-enantiomer under similar conditions. It is also possible to interconvert short chain 2-methyl-3-oxoalkanoates effecting an overall stereo-inversion of the C-2 centre. On prolonged exposure to G. candidum, syn (2R, 3S) ethyl 2-methyl-3-hydroxybutanoate 11 was converted, via the 3-oxoester 12, to the anti (2S,3S) compound 11 with an e.e. of 97% in around 23 h (Scheme 6). 

Complete enantiomer discrimination and asymmetric deactivation of the racemic XylBINAP-RuCl2(dmf) ( )-7b using DM-DABN as a chiral poison are shown to be effective in the kinetic resolution of 2-cyclohexenol (Scheme 8.9). Use of just a 0.5 molar amount of (5)-DM-DABN relative to ( )-7b gives enantiopure (S)-2-cyclohexenol, which is kinetically resolved in the same conversion as enantiopure 7b. Indeed, the relative rate of hydrogenation of (R)- versus (5)-2-cyclohexenol in the presence of only a 0.5 molar amount of (5)-DM-DABN relative to ( )-7b is significantly large (kf/kg = 102). The combination of ( )-7b with (S)-DM-DABN also gives 99.3% ee of (R)-methyl 3-hydroxybutanoate quantitatively... 

The stability of the enolates 13, derived from 1,3-dioxan-4-ones 12, is unexpectedly high enough for them to be alkylated93. At — 40°C after 2 hours more than 60% of the enolate 13 (R1 = CH3) is still present. Methylation of this enolate shows an even higher diastereoselectivity than methylation of the dianion of ethyl /i-hydroxybutanoate (Section 1.1.1.3.2.1.1.1.2.). 

TITANOCENE-CATALYZED SYNTHESIS OF METHYL 4-DEUTERIO-4-PHENYL-4-HYDROXYBUTANOATE... 

It has been stated that (-F)-tartaric acid is fully described" by the D-config-uration because, if either asymmetric carbon is reduced to a CH2 group, d -2-hydroxy-butanedioic acid is formed. Which configuration would be assigned to (+)-tartaric acid, if either one of the carboxyls were reduced to a methyl group, the hydroxyl next to the remaining carboxyl reduced to CH2, and the product compared to D- and l-3-hydroxybutanoic acids ... 

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