Diisobutylaluminumhydride → (5-Iodo-2-triisopropylsilanyloxy-phenyl)-methanol

A solution of Intermediate 61a (2.88 g, 6.60 mmol) in DCM (50 mL) at 0° C. under N2 was treated dropwise with diisobutyl aluminium hydride (1.0M in THF, 16.6 mL, 16.6 mmol) and the mixture was stirred at RT overnight. The mixture was cooled to 0° C., then treated dropwise with another portion of diisobutyl aluminium hydride (1.0M in THF, 8.3 mL, 8.30 mmol) and stirred at RT for 1 h. The mixture was cooled to 0° C. and quenched by dropwise addition of water to give a gel that was partitioned between EtOAc/ether and brine/water/aqueous potassium sodium tartrate solution. The insoluble salts were filtered off and the phases separated. The aqueous phase was extracted with EtOAc (2×) and the combined organic layers were washed with a 10% aqueous citric acid solution, saturated sodium bicarbonate solution and brine, dried (Na2SO4), filtered and evaporated in vacuo. The residue was pre-adsorbed onto diatomaceous earth and purified by FCC, using 0-15% EtOAc in cyclohexane, to give the title compound as a colorless oil (1.04 g, 39%). LCMS (Method 3): Rt 5.29 min, m/z 405 [MH+].

1. temperatureThe mixture was cooled to 0° C.
2. stirringstirred at RT for 1 h
3. temperatureThe mixture was cooled to 0° C.
4. customquenched by dropwise addition of water
5. customto give a gel that
6. customwas partitioned between EtOAc/ether and brine/water/aqueous potassium sodium tartrate solution
7. filtrationThe insoluble salts were filtered off
8. customthe phases separated
9. extractionThe aqueous phase was extracted with EtOAc (2×)
10. washthe combined organic layers were washed with a 10% aqueous citric acid solution, saturated sodium bicarbonate solution and brine
11. dry with materialdried (Na2SO4)
12. filtrationfiltered
13. customevaporated in vacuo
14. custompurified by FCC

ORD record

ord-1100536bb7104000a14be99016408b0c

Source dataset

uspto-grants-2016_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09440974B2