methyl 4-hydroxy-3,5-dimethylbenzoate

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The title compound was prepared according to Example 4, intermediate, from 2-cyclohexyl-2-[2-(2,6-dimethoxy-pyridin-3-yl)-5,6-difluoro-benzoimidazol-1-yl]-ethanol (Example 73, intermediate b), 4-hydroxy-3,5-dimethyl-benzoic acid methyl ester (commercially available), tri-N-butylposphine and N′N′N′N-tetramethylazodicarboxamide. The resulting powder was purified by silica gel chromatography using a MPLC system (CombiFlash Companion, Isco Inc.) eluting with a gradient of n-heptane:tert-butyl methyl ether (100:0 to 50:50) to give the desired compound as an off-white solid (27%). MS (Turbo Spray): m/z=580.3 [M+H]. The title compound was prepared The resulting powder was purified by silica gel chromatography eluting with a gradient of n-heptane:tert-butyl methyl ether (100:0 to 50:50)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The title compound was prepared in analogy to Example 4, intermediate, from 2-[2-(4-chloro-phenyl)-5,6-difluoro-benzoimidazol-1-yl]-2-cyclohexyl-ethanol (Example 1, intermediate c), 4-hydroxy-3,5-dimethyl-benzoic acid methyl ester and replacing di-ethyl azodicarboxylate by di-tert-butyl azodicarboxylate and a reaction time of 18 h. Light yellow solid (12%). MS (Turbo Spray): m/z=553.3 [M+H]. a reaction time of 18 h

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 2-[2-(4-chloro-phenyl)-2,4,5,6-tetrahydro-cyclopentapyrazol-3-yl]-2-cyclohexyl-ethanol (100 mg, 290 umol) in THF (2 ml) was added 4-hydroxy-3,5-dimethyl-benzoic acid methyl ester (57 mg, 319 umol; CAS Reg. No. 34137-14-9) and tri-phenylphosphine (91 mg, 348 umol) at ambient temperature under an argon atmosphere. The mixture was cooled to 0° C., di-tert-butyl azodicarboxylate (80 mg, 348 umol) was added and the suspension was stirred for 48 h at ambient temperature. The solvent was removed under reduced pressure to give a solid which was purified by preparative HPLC on reversed phase eluting with a gradient of acetonitrile/water to obtain the title compound (19 mg, 37 umol; 13%) as yellow solid. MS: m/e=507.2 [M+H+]. at ambient temperature The solvent was removed under reduced pressure to give a solid which was purified by preparative HPLC on reversed phase eluting with a gradient of acetonitrile/water

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The title compound was prepared according to Example 4, intermediate, from 2-cyclohexyl-2-[2-(2,6-dimethoxy-pyridin-3-yl)-5,6-difluoro-benzoimidazol-1-yl]-ethanol (Example 73, intermediate b), 4-hydroxy-3,5-dimethyl-benzoic acid methyl ester (commercially available), tri-N-butylposphine and N′N′N′N-tetramethylazodicarboxamide. The resulting powder was purified by silica gel chromatography using a MPLC system (CombiFlash Companion, Isco Inc.) eluting with a gradient of n-heptane:tert-butyl methyl ether (100:0 to 50:50) to give the desired compound as an off-white solid (27%). MS (Turbo Spray): m/z=580.3 [M+H]. The title compound was prepared The resulting powder was purified by silica gel chromatography eluting with a gradient of n-heptane:tert-butyl methyl ether (100:0 to 50:50)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The title compound was prepared according to Example 4, intermediate, from 2-cyclohexyl-2-[2-(2,6-dimethoxy-pyridin-3-yl)-5,6-difluoro-benzoimidazol-1-yl]-ethanol (Example 73, intermediate b), 4-hydroxy-3,5-dimethyl-benzoic acid methyl ester (commercially available), tri-N-butylposphine and N′N′N′N-tetramethylazodicarboxamide. The resulting powder was purified by silica gel chromatography using a MPLC system (CombiFlash Companion, Isco Inc.) eluting with a gradient of n-heptane:tert-butyl methyl ether (100:0 to 50:50) to give the desired compound as an off-white solid (27%). MS (Turbo Spray): m/z=580.3 [M+H]. The title compound was prepared The resulting powder was purified by silica gel chromatography eluting with a gradient of n-heptane:tert-butyl methyl ether (100:0 to 50:50)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The title compound was prepared in analogy to Example 4, intermediate, from 2-[2-(4-chloro-phenyl)-5,6-difluoro-benzoimidazol-1-yl]-2-cyclohexyl-ethanol (Example 1, intermediate c), 4-hydroxy-3,5-dimethyl-benzoic acid methyl ester and replacing di-ethyl azodicarboxylate by di-tert-butyl azodicarboxylate and a reaction time of 18 h. Light yellow solid (12%). MS (Turbo Spray): m/z=553.3 [M+H]. a reaction time of 18 h

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A 270 g quantity of methyl 4-hydroxy-3,5-dimethylbenzoate is heated in 300 ml of ethanolamine for 6 hours at a bath temperature of 160° C. while simultaneously removing the methanol which forms by distillation. The excess ethanolamine is removed under vacuum. The glassy product is ground, screened (1 mm screen), and dried thoroughly at 0.5 torr and 60° C. for a yield of 307 g. while simultaneously removing the methanol which forms by distillation The excess ethanolamine is removed under vacuum dried thoroughly at 0.5 torr and 60° C. for a yield of 307 g