Ethyl tartrate, reactions

The chiral diol 5291 (Scheme 15), obtained from ethyl tartrate in one step (75%), was used to obtain the intermediate five-membered ring cyclic sulfite. The reaction... 

Fluorination of ethyl tartrate using SF4 at ca. 25 C affords the monofluoro-derivative (41 %), whereas reaction at elevated temperatures gives the 2,3-difluoro-compound (38%), a convenient precursor of the corresponding acid and of mono-fluorofumaric acid (see Scheme 33). ... 

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. 

D. Tris[(2-peiiluorohexyl)ethyl]tin hydride (Note 7). A 1-L, three-necked flask and a stirring bar are dried in an oven. The fluorous tin bromide (13.8 g, 11.1 mmol) is dissolved in dry ether (275 mL) and transferred to the dried three-necked flask equipped with a thermometer, stirring bar, and an outlet to argon. The solution is cooled to O C. AIM solution of iithium aluminum hydride (LAH) in ether (11.1 mL, 11.1 mmol) is added dropwise over 45 min to the solution. The addition rate is adjusted to maintain a temperature between 0° and 1°C. The reaction mixture is stirred for 6 hr at 0°C. Water (75 mL) is slowly added (initially dropwise) with stirring to the ice-cold mixture. Sodium potassium tartrate (20%) (250 mL) is added and the mixture is transferred to a 1-L separatory funnel. The ethereal layer is separated and the aqueous layer is extracted three times with ether (3 x 100 mL). The combined extracts are dried with magnesium sulfate and vacuum filtered into a 1-L, round-bottomed flask. The solvent is evaporated under reduced pressure. The cmde product is distilled under a reduced pressure of 0.02 mm at 133-140°C to provide 11.3 g (9.69 mmol, 87%) of the pure product as an oil (Notes 8 and 9). 

Thus, treatment of the benzamide (35-1) from 2-phenethylamine with phosphorus oxychloride probably results in an initial formation of a transient enol chloride this then cycUzes to (35-2) under reaction conditions. The imine is then reduced with sodium borohydride. Resolution by means of the tartrate salt affords (35-3) in optically pure form. Acylation of that intermediate with ethyl chloroformate leads to carbamate (35-4). Reaction of this last with the anion from chiral quiniclidol (35-5) interestingly results in the equivalent of an ester interchange. There is thus obtained the anticholinergic agent solifenacin (35-6) [40]. 

The mixture is stirred for 2.5 h in the cold. The cold reaction mixture is then treated cautiously with a saturated solution of sodium potassium tartrate in water and stirred for 10 min in the cold. This mixture is extracted with EtOAc. The pooled ethyl acetate extracts are washed with brine, dried (Na2S04) and concentrated in vacuo to give a solid. The aqueous residue from the above extractions is diluted with 10 ml of water and extracted with ethyl acetate. 

Mild treatment of dimethyl (+ )-r,-tartratc with sulfur tetrafluoride alone gives the isolablc intermediate 2-fluoro-l, 2-bis(methoxycarbonyl)ethyl fluorosulfitc (5) in 98% yield. This can be hydrolyzed to dimethyl (- )-(2.S,.3. )-2-fluoro-3-hydroxysuccinate (6) in 97% yield. Hence, by proper choice of the reaction conditions, one or two hydroxy groups can be selectively substituted by fluorine in dialkyl tartrates." ... 

A final example of the use of tartrate-derived crotylboronates in natural product synthesis is illustrated in the formal total synthesis of ikarugamicin (Scheme II-11) [179]. Here, Roush and Wada used the asymmetric crotylboration of meso-(t/" -2,4-hexadien-1,6-dial)iron tricarbonyl 266 with (S,S)-(E)-219 to set three stereocenters in their synthesis of the a,s-indacene unit of ikarugamycin. This key reaction provided 267 in 90% yield and >98% ee. Homoallylic alcohol 267 was converted to the allylic acetate 268, which underwent stereoselective ethylation with EtsAl with retention of stereochemistry. The resulting adduct 269 was subsequently elaborated to as -indacene unit 271 through a 15-step synthetic sequence, including the intramolecular Diels-Alder reaction of 270. 

---