Sodium borohydride → [(1R,2R,3S,4R,5S)-3,4-dibenzyloxy-5-[4-chloro-3-[(4-ethoxyphenyl)methyl]phenyl]-2-hydroxy-6,8-dioxabicyclo[3.2.1]octan-1-yl]methyl acetate

Temperature

0 °C

To a solution of [(1R,3R,4R,5S)-3,4-dibenzyloxy-5-[4-chloro-3-[(4-ethoxyphenyl)methyl]phenyl]-2-oxo-6,8-dioxabicyclo[3.2.1]octan-1-yl]methyl acetate 28h (4.09 g, 6.2 mmol) in an anhydrous methanol/tetrahydrofuran mixture (v/v=3/1, 20 mL) was added sodium borohydride (278 mg, 7.5 mmol) at 0° C. The mixture was stirred at 0° C. for 5 min, then quenched with water at 0° C. and adjusted with saturated aqueous ammonium chloride till pH becomes 7. The mixture was concentrated in vacuo to remove parts of the solvent. The resulting mixture was extracted with ethyl acetate (100 mL×3). The combined organic layers were washed with saturated aqueous sodium chloride (100 mL×3), dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated in vacuo to give the title compound 28i as pale yellow oil (4.08 g, 100%). The compound was characterized by the following spectroscopic data: 1H NMR (400 MHz, DMSO-d6) δ (ppm): 7.50 (m, 2H), 7.38 (d, 3H), 7.30 (m, 3H), 7.21 (m, 3H), 7.03 (d, 2H), 6.80 (d, 2H), 6.74 (d, 2H), 5.17 (d, 1H), 4.75 (d, 1H), 4.52 (d, 1H), 4.41 (d, 1H), 4.34 (d, 1H), 4.27 (d, 1H), 4.13 (d, 1H), 3.99 (m, 2H), 3.94 (m, 3H), 3.85 (m, 3H), 3.71 (d, 1H), 2.01 (s, 3H), 1.28 (t, 3H).

1. customquenched with water at 0° C.
2. concentrationThe mixture was concentrated in vacuo
3. customto remove parts of the solvent
4. extractionThe resulting mixture was extracted with ethyl acetate (100 mL×3)
5. washThe combined organic layers were washed with saturated aqueous sodium chloride (100 mL×3)
6. dry with materialdried over anhydrous sodium sulfate
7. filtrationfiltered
8. concentrationThe filtrate was concentrated in vacuo

ORD record

ord-f153bfcb3f304fce92a381ae77a132d6

Source dataset

uspto-grants-2016_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09394329B2