L- -Tartrate

The reaction of diethyl tartrate with sulfur tetrafluonde at 25 °C results in replacement of one hydroxyl group, whereas at 100 °C, both hydroxyl groups are replaced by fluonne to form a,a -difluorosuccinate [762] The stereochemical outcome of the fluonnation of tartrate esters is retention of configuration at one of the chiral carbon atoms and inversion of configuration at the second chiral center [163,164, 165] Thus, treatment ofdimethyl(+)-L-tartrate with sulfur tetrafluonde gives dimethyl meso-a,a difluorosuccinate as the final product [163, 164], whereas dimethyl meso tartrate is converted into a racemic mixture of D- and L-a,a -difluorosuccmates [765] (equation 80)... 

TMSCN, (—)-DIPT [diisopropyl L-tartrate], Ti(/-PrO)4, CH2CI2, 0°, 6 h, rt, 12 h, 95% yield. These conditions afford chiral cyanohydrins. ... 

The drug candidate 1 was prepared from chiral cyclopentanol 10 as shown in Scheme 7.3. Reaction of 10 with racemic imidate 17, prepared from the corresponding racemic benzylic alcohol, in the presence of catalytic TfOH furnished a 1 1 mixture of diastereomers 18 and 19 which were only separated from one another by careful and tedious chromatography. Reduction of ester 18 with LiBH4 and subsequent Swern oxidation gave aldehyde 20 in 68% yield. Reductive animation of 20 with (R)-ethyl nipecotate L-tartrate salt 21 and NaBH(OAc)3 and subsequent saponification of the ester moiety yielded drug candidate 1. 

Chiral ethyl nipecotate L-tartrate salt 21 was not available on a large scale. 

The completion of the synthesis of 1 required installation of the (R)-nipecotic moiety. The original method used (R)-ethyl nipecotate L-tartrate 21, which was commercially available, but the availability of this intermediate on multi-kilogram scale required long lead times and cost was a major factor. In addition, it was also discovered that saponification of the ethyl ester in the final stages of the synthesis, as shown in Scheme 7.3, was accompanied by small amounts of epimerization at the carboxylic acid center of 1, resulting in diastereomeric contamination of the final product. 

Azoniaspirocycles have been derived from L-tartrate for use as phase-transfer catalysts <2002TL9535>. Catalyst 158 was synthesized in a straightforward manner (Equation 36), then used for catalytic asymmetric Michael reactions an example is shown (Equation 37). 

US patent 6,720,453, Formoterol tartrate polymorph [105], A method of preparation of a highly pure salt of R,R-formoterol L-tartrate is disclosed. The process provides the most thermodynamically stable polymorph by recrystallization of a novel polymorph. 

E336 mono potassium-L-(+)-tartrate (cream of tartar). 

Figure 5.45 Cationic gemini amphiphiles having chiral counterions. TEM images of representative twisted ribbons formed by 16-2-16 tartrate (49 + 50) at 0.1% in water for various values of enantiomeric excess (a) 0 (racemate) (b) 0.5 (c) 1 (pure L) (d) 1 (pure L) in presence of 1 eq sodium L-tartrate. Bar = 100 nm. Reprinted with permission from Ref. 165. Copyright 1999 by Macmillan Magazines.

Starting from substituted allyl bis-(2,4-dimethyl-3-pentyl)-L-tartrate boronic acid, synthesis of a,/l-disubstituted tetrahydrofurans (134, n = 1) or tetrahydropyrans (134, n = 2) can be accomplished with high enantioselectivity (Scheme 3-46).79... 

In a 10 mL round-bottomed flask equipped with a magnetic stirrer bar were placed, under an argon atmosphere, anhydrous dichloromethane (2 mL) and diethyl L-tartrate (0.21 mL). 

Monoalkylation of a vic-glycol.1 Selective monoalkylation or monoacylation of the vic-glycol group of dimethyl L-tartrate is possible by conversion to the O-stannylene acetal (1) by reaction with dibutyltin oxide. The acetal is converted selectively to a mono derivative (3) by reaction with an alkyl halide or acyl chloride (excess) and CsF (about 2 equiv.). KF or Bu4NF are less effective than CsF. 

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