Diisopropylamine → Methyl (2R,3R)-3-Hydroxy-2-(4-phenylcyclohexylmethyl)butanoate

Temperature

4 °C

A solution of methyl (3R)-3-hydroxybutyrate (5.6 g, 0.047 mol) in THF (20 mL) is added dropwise to a solution of LDA prepared by dropwise addition of n-butyllithium (49.5 mL, 0.099 mol, 2 M in cyclohexane) to diisopropylamine (10.0 g, 0.099 mol) in THF (20 mL) at −78° C. After stirring at −50° C. to −40° C. for 0.5 h, a solution of 4-phenylcyclohexylmethyl iodide (14.6 g, 0.049 mol) in a mixture of HMPA (10 mL) and THF (15 mL) is added dropwise. The mixture is kept at −20° C. for 48 h, then allowed to warm to 4 ° C. and kept at that temperature for 48 h. The reaction mixture is chilled to 0° C. and quenched by dropwise addition of saturated aqueous ammonium chloride solution. The aqueous phase is extracted with ether and the combined organic phase is washed with ice-cold 0.1 M HCl, then saturated sodium chloride solution and dried over sodium sulfate. Concentration of the organic phase gives 14.6 g of crude product. Column chromatography on silica gel with hexanes-EtOAc (2:1) as eluent affords 4.18 g (31%) of methyl (2R,3R)-3-hydroxy-2-(4-phenylcyclohexylmethyl)butanoate as a pale yellow oil which solidified on standing.

1. additionis added dropwise
2. waitThe mixture is kept at −20° C. for 48 h
3. waitkept at that temperature for 48 h
4. temperatureThe reaction mixture is chilled to 0° C.
5. customquenched by dropwise addition of saturated aqueous ammonium chloride solution
6. extractionThe aqueous phase is extracted with ether
7. washthe combined organic phase is washed with ice-cold 0.1 M HCl
8. dry with materialsaturated sodium chloride solution and dried over sodium sulfate
9. customConcentration of the organic phase gives 14.6 g of crude product

ORD record

ord-0ec9c7fb567449d08cd6c0ad5dced275

Source dataset

uspto-grants-2001_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06329400B1