C(NC(C)C)(C)C.C([Li])CCC.[CH3:13][O:14][C:15]([CH:17]1[O:22][CH2:21][CH2:20][N:19]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH2:18]1)=[O:16].[CH:30](=[O:32])[CH3:31]>O1CCCC1>[CH3:13][O:14][C:15]([C:17]1([CH:30]([OH:32])[CH3:31])[O:22][CH2:21][CH2:20][N:19]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH2:18]1)=[O:16]A cooled (−78° C.) solution of N,N-diisopropylamine (1.3 mL, 9.092 mmol, dried over calcium hydride) in anhydrous tetrahydrofuran (10 mL) was treated with a solution of n-butyllithium in hexanes (3.4 mL, 8.524 mmol, 2.5 M). After stirring at −78° C. for 30 minutes, the mixture was treated with a solution of morpholine-2,4-dicarboxylic acid 4-tert-butyl ester 2-methyl ester (1.394 g, 5.683 mmol) in anhydrous tetrahydrofuran (10 mL). After stirring at −78° C. for 20 minutes, the mixture was treated with acetaldehyde (0.96 mL, 17.05 mmol). After stirring at room temperature for 1 h, the reaction was quenched at 0° C. with hydrochloric acid (1 M, 40 mL). The aqueous layer was extracted with dichloromethane (2×). The organics were combined, filtered through a phase separator and the volatiles were removed in vacuo. The residue was purified by silica gel chromatography using a 50 g Isolute cartridge eluted with a continuous gradient of iso-hexanes/ethyl acetate 1:0 to 3:2 to afford the title compound (1.476 g, 90%) as a yellow oil and as a 2:1 mixture of diastereoisomers.
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