Propargyl alcohol → HCID 18616195, compound

To a solution of propargyl alcohol (67, Aldrich, 1.46 mL, 25 mmol) in anhydrous tetrahydrofuran (10 mL), was added 0.5M 9-BBN in THF (Aldrich, 100 mL, 50 mmol) through an addition funnel at 0° C. under nitrogen over a period of 1 hour. After the addition was complete, the flask with the reaction mixture was stored in a 5° C. refrigerator under nitrogen for 18 hours. The reaction mixture was warmed to room temperature under nitrogen. To the reaction mixture was added 4-bromotolunitrile (compound 61, Aldrich, 5.88 g, 30 mmol), tetrakis(triphenyl-phosphine)palladium (0) (Aldrich, 1.00 g, 0.86 mmol), and 2M sodium hydroxide solution (25 mL, 50 mmol). The reaction mixture was degassed with nitrogen three times, and then refluxed at 65° C. for 2 hours. The reaction mixture was cooled to room temperature. To that solution was added slowly 30% hydrogen peroxide in water (30 mL) and 2M sodium hydroxide solution (10 mL). A lot of gas was released during addition of hydrogen peroxide. The resulting solution was stirred at room temperature for an additional hour. The reaction mixture was extracted with ethyl acetate. The combined extracts were washed with brine and then dried over Na2SO4. After filtration and evaporation, the crude product was purified on a silica gel column, eluting with hexane-ethyl acetate (4:1 and 3:1). The product 68 was obtained as colorless oil (1.05 g, 24% yield). TLC Rf 0.30 (Hexane:EtOAc 1:1); 1H-NMR (400 MHz, CDCl3): δ 7.58 (d, 2H, J 8.1 Hz), 7.29 (d, 2H, J 8.1 Hz), 5.82 (dt, 1H, J 15.6 Hz, J 6.4 Hz), 5.71 (dt, 1H, J 15.6 Hz, J 5.4 Hz), 4.14 (d, 2H, J 5.4 Hz), 3.44 (d, 2H, J 6.4 Hz), 1.62 (s, 1H).

1. additionAfter the addition
2. customwas stored in a 5° C.
3. customfor 18 hours
4. customThe reaction mixture was degassed with nitrogen three times
5. temperaturerefluxed at 65° C. for 2 hours
6. temperatureThe reaction mixture was cooled to room temperature
7. additionTo that solution was added slowly 30% hydrogen peroxide in water (30 mL) and 2M sodium hydroxide solution (10 mL)
8. additionA lot of gas was released during addition of hydrogen peroxide
9. extractionThe reaction mixture was extracted with ethyl acetate
10. washThe combined extracts were washed with brine
11. dry with materialdried over Na2SO4
12. filtrationAfter filtration and evaporation
13. customthe crude product was purified on a silica gel column
14. washeluting with hexane-ethyl acetate (4:1 and 3:1)

ORD record

ord-f88c5fdbcd85420187d43745061e1f73

Source dataset

uspto-grants-2003_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06506754B1