(4-tert-butylphenyl)methanol

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

Procedure: To a solution of 4-chloro-5-methoxypyrimidine (1.5 g, 10.3 mmol) described in Journal of the Chemical Society (1960), 4590, and 4-t-butylbenzylalcohol (2.55 g, 15.6 mmol) in dimethylacetamide (10 mL) was added sodium hydride (0.625 g, 15.6 mmol) at 0° C., and the mixture was stirred at room temperature for 3 hrs. The reaction mixture was poured into ice water, and extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate, and the solvent was concentrated under reduced pressure. The residue was purified by silica gel column chromatography to give 4-(4-t-butylbenzyloxy)-5-methoxypyrimidine (2.16 g). extracted with ethyl acetate The organic layer was dried over anhydrous magnesium sulfate the solvent was concentrated under reduced pressure The residue was purified by silica gel column chromatography

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

Procedure: The title compound was prepared from 4-(tert-butyl)-benzyl alcohol and epichlorohydrin according to the procedures employed for the preparation of the compound in Step 1 of Example 2. employed for the preparation of the compound in Step 1 of Example 2

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

Procedure: To a solution of 4-tert-butylbenzyl alcohol (1.97 g, 12 mmol) in DCM (30 mL) was added pyridine (1.3 mL) and then a solution of 4-nitrophenyl chloroformate (1.57 g, 7.8 mmol) in DCM (20 mL). The mixture was stirred at room temperature for 1 h, concentrated under reduced pressure, and to the residue was added a mixture of of 4,5,6,7-tetrahydromidazo[4,5-c]pyridine (1.5 g, 7 mmol), methanol (3.3 mL), DMF (30 mL), and diisopropylethylamine (4.1 mL). The resulting mixture was stirred at room temperature overnight and concentrated under reduced pressure. The residue was distributed between water and ethyl acetate, phases were separated, and the organic layer was washed with water, dried (MgSO4), and filtered. A solution of oxalic acid (0.63 g) in ethyl acetate was added to the filtrate and the mixture was allowed to stand for 24 h. Filtration yielded the title compound as colorless solid. concentrated under reduced pressure to the residue was added The resulting mixture was stirred at room temperature overnight concentrated under reduced pressure were separated the organic layer was washed with water dried (MgSO4) filtered A solution of oxalic acid (0.63 g) in ethyl acetate was added to the filtrate to stand for 24 h Filtration

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

Procedure: To a solution of 4-tert-butylbenzyl alcohol (1.97 g, 12 mmol) in DCM (30 mL) was added pyridine (1.3 mL) and then a solution of 4-nitrophenyl chloroformate (1.57 g, 7.8 mmol) in DCM (20 mL). The mixture was stirred at room temperature for 1 h, concentrated under reduced pressure, and to the residue was added a mixture of of 4,5,6,7-tetrahydromidazo[4,5-c]pyridine (1.5 g, 7 mmol), methanol (3.3 mL), DMF (30 mL), and diisopropylethylamine (4.1 mL). The resulting mixture was stirred at room temperature overnight and concentrated under reduced pressure. The residue was distributed between water and ethyl acetate, phases were separated, and the organic layer was washed with water, dried (MgSO4), and filtered. A solution of oxalic acid (0.63 g) in ethyl acetate was added to the filtrate and the mixture was allowed to stand for 24 h. Filtration yielded the title compound as colorless solid. concentrated under reduced pressure to the residue was added The resulting mixture was stirred at room temperature overnight concentrated under reduced pressure were separated the organic layer was washed with water dried (MgSO4) filtered A solution of oxalic acid (0.63 g) in ethyl acetate was added to the filtrate to stand for 24 h Filtration

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

Procedure: To a solution of 4-chloro-5-methoxypyrimidine (1.5 g, 10.3 mmol) described in Journal of the Chemical Society (1960), 4590, and 4-t-butylbenzylalcohol (2.55 g, 15.6 mmol) in dimethylacetamide (10 mL) was added sodium hydride (0.625 g, 15.6 mmol) at 0° C., and the mixture was stirred at room temperature for 3 hrs. The reaction mixture was poured into ice water, and extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate, and the solvent was concentrated under reduced pressure. The residue was purified by silica gel column chromatography to give 4-(4-t-butylbenzyloxy)-5-methoxypyrimidine (2.16 g). extracted with ethyl acetate The organic layer was dried over anhydrous magnesium sulfate the solvent was concentrated under reduced pressure The residue was purified by silica gel column chromatography

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

Procedure: To a solution of 4-chloro-5-methoxypyrimidine (1.5 g, 10.3 mmol) described in Journal of the Chemical Society (1960), 4590, and 4-t-butylbenzylalcohol (2.55 g, 15.6 mmol) in dimethylacetamide (10 mL) was added sodium hydride (0.625 g, 15.6 mmol) at 0° C., and the mixture was stirred at room temperature for 3 hrs. The reaction mixture was poured into ice water, and extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate, and the solvent was concentrated under reduced pressure. The residue was purified by silica gel column chromatography to give 4-(4-t-butylbenzyloxy)-5-methoxypyrimidine (2.16 g). extracted with ethyl acetate The organic layer was dried over anhydrous magnesium sulfate the solvent was concentrated under reduced pressure The residue was purified by silica gel column chromatography

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

Procedure: The title compound was prepared from 4-(tert-butyl)-benzyl alcohol and epichlorohydrin according to the procedures employed for the preparation of the compound in Step 1 of Example 2. employed for the preparation of the compound in Step 1 of Example 2

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

Procedure: From 4-t-butylbenzyl alcohol (5.0 g; 30 mmol) and 5-amino-4-oxopentanoic acid hydrochloride (1.0 g; 6.0 mmol). The reaction was complete after 2 days. The yield was 0.84 g (52%).

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

Procedure: From 4-t-butylbenzyl alcohol (5.0 g; 30 mmol) and 5-amino-4-oxopentanoic acid hydrochloride (1.0 g; 6.0 mmol). The reaction was complete after 2 days. The yield was 0.84 g (52%).

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

Procedure: From 4-t-butylbenzyl alcohol (5.0 g; 30 mmol) and 5-amino-4-oxopentanoic acid hydrochloride (1.0 g; 6.0 mmol). The reaction was complete after 2 days. The yield was 0.84 9 (52%).

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

Procedure: To a stirred solution of oxalyl dichloride (100ml) in diethylether (500 ml) at -10° under nitrogen a solution of 4-t-butylbenzyl alcohol (200 ml) in diethylether (100 ml) was added dropwise so as to maintain the temperature between -10° and -5°. The solvent was then evaporated under vacuum to give the title compound (289 g,) as a clear oil (b.p. 120°-122° at 2 mbar). to maintain the temperature between -10° and -5° The solvent was then evaporated under vacuum

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

Procedure: From 4-t-butylbenzyl alcohol (5.0 g; 30 mmol) and 5-amino-4-oxopentanoic acid hydrochloride (1.0 g; 6.0 mmol). The reaction was complete after 2 days. The yield was 0.84 g (52%).