Dichloromethane → HCID 131732777, compound

Temperature

0 °C

A solution of the commercially available (S,S) dioxaborolane ligand (7.37 g, 27.3 mmol) in DCM (20 mL) was added. The mixture was stirred for 10 minutes. The precipitate dissolves yielding a clear solution. A solution of the alkene from step B of this example (8.53 g, 22.7 mmol) in DCM (20 mL) was added. The solution was warmed to 0° C. and stirred for 24 hours. The solution remains clear after stirring for 24 hours. The reaction was quenched after 24 hr by addition of 50 ml of sat'd aq. NH4Cl. The mixture was placed in a separatory funnel, 250 ml DCM and 200 ml 10% HCl (aq) added, shaken, and the layers separated. The aqueous layer was re-extracted with DCM (2×150 ml), the organic layers combined, transferred to a Morton flask. 2N NaOH (300 ml) and 50 ml of 30% H2O2 were added. The biphasic solution was stirred vigorously for 12 hours. The layers were separated and the aqueous phase was re-extracted with DCM (2×150 ml), the organic phases were combined, washed with 10% HCl (aq, 250 ml), 1N Na2S2O3 (250 ml), sat'd NaHCO3 (250 ml), brine (250 ml), dried over MgSO4, filtered and stripped. The material was purified by chromatography on SiO2 eluting with 30% EtOAc:Hexanes. The desired product is obtained as a mixture with the minor diastereomer and the residual SM. The desired diastereomer was isolated by Chiralpak IA stationary phase chromatography.

1. dissolutionThe precipitate dissolves
2. customyielding a clear solution
3. stirringstirred for 24 hours
4. stirringafter stirring for 24 hours
5. customThe reaction was quenched after 24 hr by addition of 50 ml of sat'd aq. NH4Cl
6. customThe mixture was placed in a separatory funnel
7. addition250 ml DCM and 200 ml 10% HCl (aq) added
8. stirringshaken
9. customthe layers separated
10. extractionThe aqueous layer was re-extracted with DCM (2×150 ml)
11. addition2N NaOH (300 ml) and 50 ml of 30% H2O2 were added
12. stirringThe biphasic solution was stirred vigorously for 12 hours
13. customThe layers were separated
14. extractionthe aqueous phase was re-extracted with DCM (2×150 ml)
15. washwashed with 10% HCl (aq, 250 ml), 1N Na2S2O3 (250 ml), sat'd NaHCO3 (250 ml), brine (250 ml)
16. dry with materialdried over MgSO4
17. filtrationfiltered
18. customThe material was purified by chromatography on SiO2 eluting with 30% EtOAc

ORD record

ord-9750ce6c5bc343a78f099b2d6d010e2e

Source dataset

uspto-grants-2015_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09018224B2