Triisopropyl borate → HCID 46739418, compound

To a solution of 3-bromo-5-(4-methoxy-benzyloxy)-pyridine (300 mg) in THF (10 mL) was added triisopropyl borate (0.28 mL) and the mixture cooled to −78° C. Then n-butyllithium (0.49 mL of a 2.5 M solution in hexanes) was added maintaining the temperature below −65° C. The reaction mixture was then allowed to warm to −20° C. over 1 h and then quenched with 2 M aqueous hydrochloric acid (2 mL). The mixture was allowed to warm to room temperature over 1 h and then diluted with water (25 mL), the pH was adjusted to 7 and then extracted into ethyl acetate (3×25 mL). The combined organics were washed with brine (20 mL), dried (MgSO4) and reduced in vacuo. A mixture of the crude product and pinacol (236 mg) in toluene (15 mL) was then heated at reflux for 4 h. The mixture was then reduced in vacuo, dissolved in ethyl acetate (30 mL) and washed with water (2×30 mL) and brine (30 mL). The combined organics were dried (MgSO4) and reduced in vacuo to give 3-(4-methoxy-benzyloxy)-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-pyridine as an off-white solid (162 mg).

1. temperaturemaintaining the temperature below −65° C
2. temperatureto warm to −20° C. over 1 h
3. customquenched with 2 M aqueous hydrochloric acid (2 mL)
4. temperatureto warm to room temperature over 1 h
5. additiondiluted with water (25 mL)
6. extractionextracted into ethyl acetate (3×25 mL)
7. washThe combined organics were washed with brine (20 mL)
8. dry with materialdried (MgSO4)
9. additionA mixture of the crude product and pinacol (236 mg) in toluene (15 mL)
10. temperaturewas then heated
11. temperatureat reflux for 4 h
12. dissolutiondissolved in ethyl acetate (30 mL)
13. washwashed with water (2×30 mL) and brine (30 mL)
14. dry with materialThe combined organics were dried (MgSO4)

ORD record

ord-5ef0781c0bd745ae8fe044cb87b87902

Source dataset

uspto-grants-2014_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08802670B2