Lithiumtriethylborohydride → HCID 71553880, compound

Temperature

-78 °C

A flame-dried flask was charged with SEM dilactam 13 (109 mg, 109 μmol, 1 eq) dissolved in anhydrous tetrahydrofuran (2.2 mL), and cooled to −78° C. Lithium triethylborohydride (0.33 mL of a 1 M solution in THF, 330 μmol, 3 eq) was added dropwise and the reaction was stirred under nitrogen for 2.5 hours, at which time LC revealed incomplete conversion to product. An additional 0.66 mL of reductant was added and the reaction was stirred for one more hour. The reaction was quenched through the addition of water (1 mL) and allowed to warm to room temperature, then diluted brine (25 mL) and extracted three times with dichloromethane (25 mL). The combined organics were washed with brine (25 mL), dried over sodium sulfate, and evaporated to dryness. The residue was dissolved in a mixture of dichloromethane (2.8 mL), ethanol (7.4 mL), and water (1.0 mL), and silica gel (2.7 g) was added. The resulting slurry was stirred at room temperature for 4 days. TLC analysis revealed conversion to imine dimer 14, at which time the slurry was filtered over a sintered glass funnel and the silica gel cake was washed with 10% methanol in chloroform until no further PBD absorbance was observed in the filtrate. Concentration of the filtrate provided crude imine dimer 14. The material was dissolved in minimal dichloromethane and purified by radial chromatography on a 1 mm chromatotron plate eluted with CH2Cl2/MeOH mixtures (100:0 to 80:20) to provide 14 (31 mg, 40%). LC-MS: tR 8.48 min, m/z (ES+) found 712.2 (M+H)+.

1. additionAn additional 0.66 mL of reductant was added
2. stirringthe reaction was stirred for one more hour
3. customThe reaction was quenched through the addition of water (1 mL)
4. temperatureto warm to room temperature
5. extractiondiluted brine (25 mL) and extracted three times with dichloromethane (25 mL)
6. washThe combined organics were washed with brine (25 mL)
7. dry with materialdried over sodium sulfate
8. customevaporated to dryness
9. dissolutionThe residue was dissolved in a mixture of dichloromethane (2.8 mL), ethanol (7.4 mL), and water (1.0 mL), and silica gel (2.7 g)
10. additionwas added
11. stirringThe resulting slurry was stirred at room temperature for 4 days
12. filtrationat which time the slurry was filtered over a sintered glass funnel
13. washthe silica gel cake was washed with 10% methanol in chloroform until no further PBD absorbance
14. customConcentration of the filtrate provided crude imine dimer 14
15. custompurified by radial chromatography on a 1 mm chromatotron plate
16. washeluted with CH2Cl2/MeOH mixtures (100:0 to 80:20)

ORD record

ord-78b0353096f849f79c3a3a96e17200af

Source dataset

uspto-grants-2016_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09387259B2