Sodium Hydroxide → tert-Butyl ((2S)-1-hydroxy-3-((tetrahydro-2H-pyran-2-yl)oxy)propan-2-yl)carbamate

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Reaction Steps

To a 3 L three neck flask fitted with a thermometer, magnetic stirrer, under argon was added 2 (128 g, 0.42 mol) in diethyl ether (1.5 L). A clear yellow solution formed after one hour of stirring at room temperature. The solution was cooled to 10° C. with an ice/water bath. Lithium borohydride (9.3 g, 0.42 mol) was added in three portions over 30 minutes to keep the temperature below 18° C. The reaction mixture was warmed to 32° C. and was complete after 60 min by TLC (EtOAc:Hexanes; 3:7, anisaldehyde dip reagent). The reaction mixture was transferred to a 4 L flask and stirred vigorously while 1M NaOH (350 mL) was added slowly to pH 11 and stirred an additional 30 min. Ethyl acetate (500 mL) was added to the mixture and stirred 5 min. The layers were separated. The organic layer was washed with brine (1×600 mL) and dried over granular Na2SO4 (100 g) for 15 min. The mixture was filtered and concentrated under reduced pressure overnight to 109 g (94%) of product 3 as a waxy white crystalline solid. 1H NMR (60 MHz, CDCl3) δ 5.0-5.3 (br m, 1H), 3.2-4.6 (m, 8H), 2.4-3.0 (m, 1H), 1.3-1.7 (m, 15H).

Provenance & Evidence