Dimethylformamide → 2-Hydroxy-3-(2-nitrophenyl)propanoic acid
Reaction equation
CN(C)C=O.S(Cl)(Cl)=O.[N+:10]([C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=1[CH2:19][C:20](=[O:24])[C:21]([OH:23])=[O:22])([O-:12])=[O:11]>>[OH:24][CH:20]([CH2:19][C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][C:13]=1[N+:10]([O-:12])=[O:11])[C:21]([OH:23])=[O:22]Participants
4
Procedure
To magnetically stirred N,N-dimethylformamide (23 ml., 297.3 mmol) cooled in ice was slowly added dropwise thionyl chloride (139 ml., ca. 1.91 mol). A solution of (+)-α-hydroxy-2-nitrobenzenepropanoic acid [11.60 g., 54.9 mmol, [α]D25 +49.94° (c 2.465, 95% EtOH)], obtained from the chiral reduction of 2-nitro-α-oxobenzenepropanoic acid described in Example 1, in dichloromethane (133 ml.) was then added dropwise to the cold Vilsmeier reagent. The ice bath was removed and the solution, protected from moisture, was left at room temperature (25° C.) for 18 hours. The resulting yellow solution was evaporated to syrup. The syrup was dissolved in dichloromethane and the solution was poured cautiously onto stirred ice. The mixture was stirred for one hour during which time it warmed to room temperature. The organic phase was separated, washed (×3) with water and dried (MgSO4). Evaporation gave a syrup which was subjected to an oil pump vacuum for 0.5 hour. The syrup was dissolved in ether and 2,6-dimethylpiperidine was added to approximate neutrality (ca. pH 8 by pH paper). The crude titled compound (12.40 g., 66%) crystallized readily, m.p. 148°-153° C. Three crystallizations (with decolorization) from methanol-ether gave 6.01 g. (32% of pure product, m.p. 164°-167° C. dec., [α]D25 -41.49° (c 1.005, 95% EtOH).