ethyl 8-forMyl-1,4-dioxaspiro[4.5]decane-8-carboxylate

1489-97-0

109-94-4

1006686-08-3

Step 2: Preparation of ethyl 8-formyl-1,4-dioxaspiro[4.5]decane-8-carboxylate. To a solution of ethyl 1,4-dioxaspiro[4.5]decane-8-carboxylate (32.31 g, 151 mmol) in anhydrous THF (250 mL) at -78 °C under nitrogen protection was slowly added a THF solution of 2M lithium diisopropylammonium (98 mL, 196 mmol) over a period of 5 min via a constant pressure dropping funnel. The reaction mixture was stirred at -78 °C for 1 hour. Subsequently, the cold bath was replaced with an ice bath so that the reaction mixture continued to be stirred at 0 °C for 1 hour. The reaction mixture was again cooled to -78 °C and a solution of ethyl formate (18.65 mL, 226 mmol) in anhydrous THF (40 mL) was added dropwise through a constant pressure dropping funnel over 45 minutes. The reaction mixture was continued to be stirred at -78 °C for 1 hour. The cold bath was removed and a saturated aqueous NH4Cl solution (250 mL) was slowly added dropwise to the reaction mixture and stirred at room temperature for 30 min. The reaction mixture was extracted with EtOAc (3 x 300 mL) and the organic phases were combined. The organic phase was washed sequentially with 0.5N HCl (300 mL) and saturated brine, dried over anhydrous MgSO4, filtered and concentrated under reduced pressure to give a brown viscous oil. The crude product was purified by rapid column chromatography on silica gel (750 g silica gel, gradient elution: 9:1 to 5:1 hexane/EtOAc) to isolate the recovered starting material, ethyl 1,4-dioxaspiro[4.5]decane-8-carboxylate (8.6 g, 40.1 mmol, 26.6% yield), and the target product, 8-formyl-1,4-dioxaspiro[4.5]decane-8-carboxylic acid (20.6 g, 20.5 mmol). carboxylic acid ethyl ester (20.1 g, 83 mmol, 55.0% yield), both as yellow viscous oil. The 1H NMR (400 MHz, CDCl3) data of the target product were as follows: δ9.50 (s, 1H), 4.17 (q, J=7.2 Hz, 2H), 3.94-3.86 (m, 4H), 2.24-2.09 (m, 2H), 2.01 (ddd, J=13.5,8.3,5.1 Hz, 2H), 1.75- 1.48 (m, 4H), 1.23 (t, J=7.2Hz, 3H).