[Li]CCCC.[CH3:6][O:7][C:8](=[O:16])[CH2:9][C@H:10]([CH3:15])[CH2:11][C:12]([OH:14])=[O:13].Cl[C:18]([O:20][CH3:21])=[O:19].Cl>C1COCC1>[CH3:6][O:7][C:8](=[O:16])[CH:9]([C:18]([O:20][CH3:21])=[O:19])[C@H:10]([CH3:15])[CH2:11][C:12]([OH:14])=[O:13]To a 250 mL round-bottomed flask equipped with a stirbar and purged with nitrogen, was added 30 mL anhydrous THF followed by DIPA (2.21 g, 3.5 eq, 21.85 mmol). The mixture was cooled to −78° C. with stirring, n-BuLi (2.5 M, 3.3 eq, Aldrich) was then added dropwise, and the reaction was stirred for 10 min. To the flask was slowly added (R)-5-methoxy-3-methyl-5-oxopentanoic acid (1 g, 6.25 mmol, in 10.0 mL THF, Sumitomo) over about 2 min. After 30 min stirring at −78° C., a solution of methyl chloroformate (2.1 eq, 13.13 mmol) in THF (10 mL) was slowly added to the mixture. After the addition was complete, the reaction mixture was allowed warm to room temperature overnight. The reaction mixture was adjusted to about pH 5 to 6 (using pH paper), with cooling to maintain about ambient temperature using 2N aq. HCl. The reaction mixture was concentrated under reduced pressure, diluted with 75 mL EtOAc and 25 mL aq. 1N HCl. The layers were separated and the aqueous phase was extracted (2×15 mL EtOAc). The combined organics were washed with saturated aqueous NaCl (1×15 mL), dried over MgSO4, and concentrated under reduced pressure to give the product (1.36 g), which was used in the subsequent step without purification.
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