从手性氨基酸或酯经过重氮化反应（Sandmeyer反应）得到重氮盐，该盐经水解后可以得到手性羟基酸。反应后构型保持【Nature 166, 179–180 (1950). https://doi.org/10.1038/166179a0】
反应实例
To a 2 L round bottom threenecked flask, 1,4 dioxane (625 mL) was added followed by O- benzyl-L-tyrosine(50 g, 0.184 mol). To this suspension dilute aqueous sulfuric acid solution (54g, 0.553 mol, in 175 mL water) was added at ca 26-28 .deg.C. It was cooled to 0.deg.C-2 .deg.C in an ice salt BATH.. At 0 .deg.C, aqueous sodium nitritesolution (63.6 g, 0.922 mol) was added dropwise. After the addition, it was stirredfor an extended period of time (-UPTO 24 hours) below 30 .deg.C. It was dilutedwith water and extracted with ethyl acetate. Extracts were combined and washedwith water. Organic layer was collected and dried over anhydrous sodiumsulfate. It was filtered and filtrate was concentrated below 45 .deg.C todryness under reduced pressure to obtain crude semi-solid product (58.9 g). Thecrude product was purified by stirring in a mixture of diisopropyl ether ethylacetate and filtered and washed with diisopropyl ether. The product obtainedwas dried in an oven at 55 .deg.C-60 .deg.C. The product weighs about 25.7 g(51 percent yield). The IHPLC assay was 92.3 percent and enatiomeric excess was100 percent; Example 8; S (-) 2-hydroxy-3- (4-benzyloxyphenyl) propanoic acid;To a 20 L round bottom three necked flask, 1,4 dioxane (6.25 L) was addedfollowed by 0- benzyl-L-tyrosine (500G, 1.84 mol). To this suspension diluteaqueous sulfuric acid solution (540 G, 5. 53 mol, in 2.5 L water) was added atRT. It was cooled to 0 .deg.C-2 .deg.C in an ice salt bath. At 0 .deg.C,aqueous sodium nitrite solution (636 g, 9.22 mol) was added. After theaddition, it was stirred for extended period of time (-UPTO 24 hours) below 30.deg.C. It was diluted with water and extracted with ethyl acetate. Extractswere combined and washed with water. Organic layer was collected and dried overanhydrous sodium sulfate. It was filtered and filtrate was concentrated below45 .deg.C to dryness under reduced pressure to obtain crude semi-solid product(820 g). The crude product was purified by stirring in a mixture of diisopropylether & ethyl acetate. It was filtered and washed with diisopropyl ether.The dark yellowish product obtained was dried in an oven at 55 .deg.C-60.deg.C. The product weighs about 235 g (47 percent yield). The HPLC assay was98.4 percent and enatiomeric excess was 98 percent
【Patent; CADILA HEALTHCARE LIMITED; Publ.: WO2005/19152 A2 (2005/03/03),Appl.: WO2004-IN156 (2004/06/04)】
A solution of sodium nitrite (51.8 g, 720 mmol) in 200 ML of water was added dropwise over 6 hours to a stirred solution of L-phenylalanine (33.04 g,200 mmol) in 500 ML of 10percent sulfuric acid at 50.deg. C. After the additionwas complete, the reaction mixture was stirred for 3 hours at 50.deg. C, thenat room temperature overnight.. The reaction mixture was extracted with ethylacetate (3*200 ML, 2*100 ML), then the combined organic extract was washed withwater and brine, dried over sodium sulfate and evaporated to yield 28.98 g of ayellow solid. Recrystallization from benzene afforded 22.15 g of the title Acompound as white needles, m.p. 120.deg.-124.deg. C.
【Patent; E. R. Squibb and Sons, Inc.; Publ.: US5151513 A1 (1992/09/29),Appl.: US1988-187782 (1988/04/29)】
【Heterocycles 1996, 43(6), 1287-1300 】
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