[Cl-].[Al+3].[Cl-].[Cl-].CC(C)CC([O:10][C:11]1[CH2:16][C:15]([CH3:18])([CH3:17])[CH2:14][C:13](=[O:19])[CH:12]=1)=O.Cl>ClCCl.[Cl-].[Na+].O>[C:11]([OH:10])(=[C:12]1[C:11](=[O:10])[CH2:16][C:15]([CH3:17])([CH3:18])[CH2:14][C:13]1=[O:19])[CH2:16][CH:15]([CH3:17])[CH3:14]N-(ivDde)-D-serine (FIG. 3, structure C) was prepared from D-serine and ivDde-OH which was synthesized by O-acylation of dimedone with isovaleryl chloride in the presence of pyridine followed by the rearrangement of formed 5,5-dimethyl-3-oxocyclohex-1-enyl 3-methylbutanoate with aluminum chloride using a previously reported method (Akhrem, A. A., et al. Synthesis 1978, 925). In particular, a solution of isovaleryl chloride (13.5 mL, 13.3 g, 110 mmol) in dichloromethane (50 mL) was added dropwise over period of 15 min to a stirred solution of dimedone (14 g, 100 mmol) and pyridine (9.7 mL, 9.5 g, 120 mmol) in dichloromethane (150 mL). The reaction mixture was stirred for 1.5 h, and washed with 2N aqueous hydrochloric acid (2×50 mL), water, and saturated aqueous sodium bicarbonate (50 mL), and then dried over magnesium sulfate. The solvent was removed by rotary evaporator under vacuum to give 5,5-dimethyl-3-oxocyclohex-1-enyl 3-methylbutanoate (22.4 g, 100% yield) which appeared as a light yellow oil. To a stirred suspension of aluminum chloride (16.0 g, 120 mmol) in dichloromethane (100 mL) cooled on ice-bath was added dropwise a solution of 5,5-dimethyl-3-oxocyclohex-1-enyl 3-methylbutanoate (11.2 g, 50 mmol) over period of 30 min. The reaction mixture was allowed to warm to room temperature and stirred for 1 h. Then the reaction mixture was slowly poured into a mixture of 37% aqueous hydrochloric acid (50 mL) and ice (150 g) with cooling on ice so the temperature did not exceed 5° C. Brine (200 mL) was added to the mixture and the product was extracted with dichloromethane (6×50 mL, completeness of the extraction was checked by TLC). The extract was washed with brine (2×50 mL), dried over magnesium sulfate, and concentrated on rotary evaporator under vacuum. The crude product was purified by column chromatography on silica gel using gradient of hexanes going to ethyl acetate:hexanes (1:10) to give ivDde-OH (10.5 g, 94%) which appeared as a light yellow oil.
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