Aluminium lithium hydride → 2-[2-(4-Chloro-phenyl)-5,6-difluoro-benzoimidazol-1-yl]-2-(4,4-difluoro-cyclohexyl)-ethanol

To an ice-cold solution of 1.18 g (2.68 mmol) [2-(4-chloro-phenyl)-5,6-difluoro-benzoimidazol-1-yl]-(4,4-difluoro-cyclohexyl)-acetic acid in 20 ml tetrahydrofuran was added 0.15 g (4.01 mmol) lithium aluminium hydride. After removal of the cooling bath the reaction mixture was stirred for 1.25 h at room temperature. The reaction mixture was poured onto 100 ml aqueous saturated potassium sodium tartrate solution, the phases were separated and the aqueous layer was extracted three times with ethyl acetate. The combined organic layers were washed with brine, dried over magnesium sulfate, filtered and evaporated. The remaining oil was purified by silica gel chromatography using a MPLC system (CombiFlash Companion, Isco Inc.) eluting with a gradient of heptane:ethyl acetate (100:0 to 50:50). Light yellow solid (39%). MS (Turbo Spray): m/z=427.1 [M+H].

1. customAfter removal of the cooling bath the reaction mixture
2. additionThe reaction mixture was poured onto 100 ml aqueous saturated potassium sodium tartrate solution
3. customthe phases were separated
4. extractionthe aqueous layer was extracted three times with ethyl acetate
5. washThe combined organic layers were washed with brine
6. dry with materialdried over magnesium sulfate
7. filtrationfiltered
8. customevaporated
9. customThe remaining oil was purified by silica gel chromatography
10. washeluting with a gradient of heptane:ethyl acetate (100:0 to 50:50)

ORD record

ord-a9d4252e696140818dec0957c08cc5d1

Source dataset

uspto-grants-2012_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08088930B2