Water → HCID 11622478, compound

Temperature

0 °C

A 250-mL round-bottomed flask, equipped with a magnetic stirring bar and a thermometer was fitted with a septum and a nitrogen inlet. The apparatus was charged with 1.60 g (40.0 mmol) of a 60% dispersion of sodium hydride in mineral oil. The sodium hydride was washed with 3×20 mL of dry hexane and then suspended in 40 mL of dry N,N-dimethylformamide and cooled to 0° C. To the stirred suspension was added 4.32 mL (6.21 g, 36.3 mmol) of benzyl bromide followed by dropwise addition of 3.47 g (34.6 mmol) of ketone 2 (via cannula) dissolved in 10 mL of diethyl ether over 15 min maintaining the reaction temperature at 6° C. or less. The reaction mixture was stirred for 20 minutes at 0° C., then warmed to room temperature. After 12 hours, 10 mL of water was cautiously added and the mixture was transferred to a 250-mL separatory funnel. The aqueous phase was extracted with 3×100 mL of ethyl acetate. The organic layers were individually washed with 100 mL of brine, combined, dried over sodium sulfate, filtered, concentrated and chromatographed (6 cm×33 cm column, 9:1 hexane:dichloromethane) to afford 5.93 g (89%) of benzyl ether 3 as a clear, colorless liquid: Rf =0.20 (9:1 hexane:dichloromethane). [a]54622 -1.6° (c 2.21, CH2Cl2). IR (film): 3080m, 3070m, 3035m, 3005w, 2980s, 2960s, 2930s, 2910s, 2880s, 2860s, 2975w, 1645m, 1605w, 1495m, 1480w, 1455s, 1445m, 1415w, 1375m, 1365m, 1310w, 1255w, 1205w, 1160w, 1100s, 1040m, 995m, 915s, 745s, 695s, 605m. 1H-NMR: 7.36-7.24 (m, 5H, ArH); 5.85-5.72 (m, 1H, CH=CH2); 5.06-5.00 (m, 2H, CH=CH2); 4.51 (s, 2H, ArCH2O); 3.33 (dd, J=9.1, 6.2, 1H, one of CH2OBn); 3.28 (dd, J=9.1, 6.2, 1H, one of CH2OBn); 2.27-2.19 (m, 1H, CHCH3); 1.98-1.84 (m, 2H, CH2CH=CH2); 0.93 (d, J=6.5, 3H, CHCH3). 13C NMR: 138.7, 136.8, 128 2, 127.4, 127.3, 115.8, 75.2, 72.9, 38.0, 33.3, 16.7.

1. customA 250-mL round-bottomed flask, equipped with a magnetic stirring bar
2. customa thermometer was fitted with a septum and a nitrogen inlet
3. washThe sodium hydride was washed with 3×20 mL of dry hexane
4. temperaturemaintaining the reaction temperature at 6° C. or less
5. temperaturewarmed to room temperature
6. waitAfter 12 hours
7. customthe mixture was transferred to a 250-mL separatory funnel
8. extractionThe aqueous phase was extracted with 3×100 mL of ethyl acetate
9. washThe organic layers were individually washed with 100 mL of brine
10. dry with materialdried over sodium sulfate
11. filtrationfiltered
12. concentrationconcentrated
13. customchromatographed (6 cm×33 cm column, 9:1 hexane:dichloromethane)

ORD record

ord-ea673b9e38704099b863b3e0f27eadee

Source dataset

uspto-grants-1992_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05155228