Sodium borohydride → HCID 66810576, Verbindung

To a solution of 3-methylene-5-nitro-6-(2,4,5-trifluorophenyl)-3,4-dihydro-2H-pyran (798 mg, 2.94 mmol) in chloroform (42 mL) and isopropyl alcohol (7.8 mL) was added silica gel (5.1 g), and sodium borohydride (420 mg, 11.1 mmol), and the reaction mixture was stirred for 30 min at room temperature. The reaction mixture was then quenched by dropwise addition of hydrochloric acid (6 mL, 2N) and filtered. The resulting solid residue was washed with ethyl acetate (100 mL). The combined filtrate was washed successively with saturated aqueous sodium bicarbonate solution and brine, dried over anhydrous sodium sulfate, and evaporated. The resultant amber oil was dissolved in tetrahydrofuran (15 mL) and 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU, 40 μL) was added. The solution was stirred for 105 min and then transferred to a separatory funnel containing ethyl acetate (100 mL) and 1N hydrochloric acid (50 mL). The organic layer was washed with brine and the aqueous layer extracted with ethyl acetate. The combined organic layer was dried over anhydrous sodium sulfate, filtered and evaporated to yield a crude product which was purified by flash chromatography (silica gel, 8-10% ether in hexane) to yield trans-5-methylene-3-nitro-2-(2,4,5 trifluorophenyl)tetrahydro-2H-pyran. A portion of this product was resolved by HPLC (ChiralCel OD, 1.5% isopropyl alcohol in heptane) to yield the slower-moving enantiomer, (2R,3S)-5-methylene-3-nitro-2-(2,4,5-trifluorophenyl)tetrahydro-2H-pyran.

1. customThe reaction mixture was then quenched by dropwise addition of hydrochloric acid (6 mL, 2N)
2. filtrationfiltered
3. washThe resulting solid residue was washed with ethyl acetate (100 mL)
4. washThe combined filtrate was washed successively with saturated aqueous sodium bicarbonate solution and brine
5. dry with materialdried over anhydrous sodium sulfate
6. customevaporated
7. dissolutionThe resultant amber oil was dissolved in tetrahydrofuran (15 mL)
8. addition1,8-diazabicyclo[5.4.0]undec-7-ene (DBU, 40 μL) was added
9. stirringThe solution was stirred for 105 min
10. customtransferred to a separatory funnel
11. additioncontaining ethyl acetate (100 mL) and 1N hydrochloric acid (50 mL)
12. washThe organic layer was washed with brine
13. extractionthe aqueous layer extracted with ethyl acetate
14. dry with materialThe combined organic layer was dried over anhydrous sodium sulfate
15. filtrationfiltered
16. customevaporated
17. customto yield a crude product which
18. customwas purified by flash chromatography (silica gel, 8-10% ether in hexane)

ORD-Eintrag

ord-f4a411ae5ba443f98d18efc3c7ceb9b9

Quelldatensatz

uspto-grants-2013_06

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08455533B2