N-Boc-1-oxa-8-aza-spiro[4.5]decan-3-ol

954236-44-3

240401-09-6

The general procedure for the synthesis of tert-butyl 3-hydroxy-1-oxa-8-azaspiro[4.5]decane-8-carboxylate from tert-butyl 3-oxa-8-azaspiro[4.5]decane-8-carboxylate is as follows: sodium borohydride (445 mg, 11.8 mmol) was added to 3-oxo-1-oxa-8-azaspiro[4.5]decane-8-carboxylate at 0 °C in a tert-butyl ester (1.50 g, 5.88 mmol) in a methanolic solution (59 mL). The reaction mixture was stirred at 23 °C for 2 hours. Upon completion of the reaction, the solvent was removed by vacuum and the residue was partitioned between ethyl acetate and water. The aqueous layer was extracted with ethyl acetate and the combined organic layers were dried with magnesium sulfate, filtered and concentrated under reduced pressure to give a mixture of C74 and C75 as a colorless oil. The yield of the racemic product was 1.45 g (5.63 mmol, 96%).GCMS m/z 257.1 [M+].1H NMR (400 MHz, CDCl3) δ 4.54-4.48 (br m, 1H), 3.93 (dd, half of the ABX mode, J = 10.2, 4.3 Hz, 1H), 3.85-3.79 (m, 1H), 3.67-3.79 (m, 1H). 1H), 3.67-3.53 (br m, 2H), 3.40-3.28 (m, 2H), 1.97 (dd, half of ABX mode, J = 13.7, 6.2 Hz, 1H), 1.89-1.48 (m, 6H, hypothetical; partially obscured by water peaks), 1.46 (s, 9H). A portion of the racemate (1.30 g, 5.05 mmol) was separated into its component enantiomers by supercritical fluid chromatography [column: Phenomenex Lux Amylose-1,5 μm; mobile phase: 85:15 carbon dioxide/(methanol containing 0.2% ammonium hydroxide)]. The first elution product showed a negative (-) rotation and was in the form of a dendritic resin, named C74, with a yield of 650 mg (2.53 mmol, 50%). The second elution product exhibits a positive (+) rotation, is solid, named C75, and yields 620 mg (2.41 mmol, 48%).The absolute stereochemistry of C74 and C75 was determined based on the conversion of C74 to C72 (see Step 4).