[(3-Bromophenyl)methoxy](tert-butyl)dimethylsilane

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

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

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: [(3-Bromobenzyl)oxy](tert-butyl)dimethylsilane (860 mg) was mixed with THF (10 ml), followed by cooling to −78° C. under argon atmosphere. A 1.60 M n-butyl lithium/hexane solution (1.8 ml) was added dropwise thereto, followed by stirring at −78° C. for 10 minutes, and then 2-morpholin-4-ylpyrimidine-5-carboaldehyde (500 mg) was added thereto. The mixture was warmed to 0° C. over 1 hour and then stirred again at 0° C. for 1 hour. Water and EtOAc were added to the reaction mixture, and the organic layer was dried over Na2SO4 and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (hexane/EtOAc) to obtain [3-({[tert-butyl(dimethyl)silyl]oxy}methyl)phenyl][2-(morpholin-4-yl)pyrimidin-5-yl]methanol (914 mg). The mixture was warmed to 0° C. over 1 hour stirred again at 0° C. for 1 hour the organic layer was dried over Na2SO4 concentrated under reduced pressure The obtained residue was purified by silica gel column chromatography (hexane/EtOAc)

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: [(3-Bromobenzyl)oxy](tert-butyl)dimethylsilane (860 mg) was mixed with THF (10 ml), followed by cooling to −78° C. under argon atmosphere. A 1.60 M n-butyl lithium/hexane solution (1.8 ml) was added dropwise thereto, followed by stirring at −78° C. for 10 minutes, and then 2-morpholin-4-ylpyrimidine-5-carboaldehyde (500 mg) was added thereto. The mixture was warmed to 0° C. over 1 hour and then stirred again at 0° C. for 1 hour. Water and EtOAc were added to the reaction mixture, and the organic layer was dried over Na2SO4 and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (hexane/EtOAc) to obtain [3-({[tert-butyl(dimethyl)silyl]oxy}methyl)phenyl][2-(morpholin-4-yl)pyrimidin-5-yl]methanol (914 mg). The mixture was warmed to 0° C. over 1 hour stirred again at 0° C. for 1 hour the organic layer was dried over Na2SO4 concentrated under reduced pressure The obtained residue was purified by silica gel column chromatography (hexane/EtOAc)

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

Procedure: (3-Bromophenyl)methanol (5.0 g) was mixed with THF (60 ml), and TBSCl (5.0 g) and imidazole (3 g) were added thereto, followed by stirring at room temperature overnight. The reaction mixture was concentrated under reduced pressure, and water and EtOAc were added thereto. The organic layer was dried over Na2SO4 and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography to obtain [(3-bromobenzyl)oxy](tert-butyl)dimethylsilane (8.0 g). were added The reaction mixture was concentrated under reduced pressure, and water and EtOAc were added The organic layer was dried over Na2SO4 concentrated under reduced pressure The obtained residue was purified by silica gel column chromatography

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

Procedure: To a suspension of 60.0 g of 3-(tert-butyldimethylsilyloxymethyl)bromobenzene (prepared from tert-butyldimethylchlorosilane and 3-bromobenzyl alcohol according to the procedure described by Kendall P. M. et al., J. Org. Chem., 1979, 44, 1421) in 500 ml of anhydrous THF cooled to -78° C., 131 ml of 1.6M n-butyllithium in n-hexane were added under a nitrogen atmosphere and the resulting mixture was stirred for 2.5 hrs. A solution of 6.30 g of (1S,3aS,7aR)-1-hydroxymethyl-3a-hydroxy-7a-methyl-5-perhydroindenone in 60 ml of anhydrous THF was added. After 1 hr the reaction mixture was allowed to warm to 0° C., and cautiously quenched with 300 ml of 5% aqueous NaH2PO4.H2O and extracted with ethyl acetate. The organic layer was dried over sodium sulfate and evaporated to dryness under reduced pressure. The residue was purified by flash-chromatography (SiO2) with n-hexane/acetone/chloroform 6:2:2 as the eluant to give 9.62 g of (1S,3aS,5R,7aR)-1-hydroxymethyl-5-(3-tert-butyldimethylsilyloxymethylphenyl)-7a-methylperhydroinden-3a,5-diol as a white foam. After 1 hr the reaction mixture was allowed cautiously quenched with 300 ml of 5% aqueous NaH2PO4.H2O extracted with ethyl acetate The organic layer was dried over sodium sulfate evaporated to dryness under reduced pressure The residue was purified by flash-chromatography (SiO2) with n-hexane/acetone/chloroform 6:2:2 as the eluant

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

Procedure: TBSCl (18.7 g, 124.3 mmol), Et3N (14.08 g, 139.2 mmol) and DMAP (194.3 mg, 8.9 mmol) were dissolved in CH2Cl2 (120 mL) and the solution was cooled to 0-5° C. (3-Bromophenyl)methanol (18.5 g, 99.4 mmol) was added dropwise to the solution. After the addition of the (3-Bromophenyl)methanol, the mixture was warmed to room temperature and stirred for 2 h. 5% HCl was added to the reaction mixture to adjust the pH=4-5. Then the organic phase was separated and the aqueous layer was extracted with CH2Cl2 (50 mL×2). The combined organic phases were washed with water and dried over Na2SO4. After removing the solvent, 28.5 g of {[(3-bromophenyl)methyl]oxy}(1,1-dimethylethyl)dimethylsilane was obtained (Yield: 95.1%). was added dropwise to the solution Then the organic phase was separated the aqueous layer was extracted with CH2Cl2 (50 mL×2) The combined organic phases were washed with water dried over Na2SO4 After removing the solvent

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

Procedure: TBSCl (18.7 g, 124.3 mmol), Et3N (14.08 g, 139.2 mmol) and DMAP (194.3 mg, 8.9 mmol) were dissolved in CH2Cl2 (120 mL) and the solution was cooled to 0-5° C. (3-Bromophenyl)methanol (18.5 g, 99.4 mmol) was added dropwise to the solution. After the addition of the (3-bromophenyl)methanol, the mixture was warmed to room temperature and stirred for 2 h. 5% HCl was added to the reaction mixture to adjust the pH=4-5. Then the organic phase was separated and the aqueous layer was extracted with CH2Cl2 (50 mL×2). The combined organic phases were washed with water and dried over Na2SO4. After removing the solvent, 28.5 g of {[(3-bromophenyl)methyl]oxy}(1,1-dimethylethyl)dimethylsilane was obtained (Yield: 95.1%). was added dropwise to the solution Then the organic phase was separated the aqueous layer was extracted with CH2Cl2 (50 mL×2) The combined organic phases were washed with water dried over Na2SO4 After removing the solvent

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

Procedure: TBSCl (18.7 g, 124.3 mmol), Et3N (14.08 g, 139.2 mmol) and DMAP (194.3 mg, 8.9 mmol) were dissolved in CH2Cl2 (120 mL) and the solution was cooled to 0-5° C. (3-Bromophenyl)methanol (18.5 g, 99.4 mmol) was added dropwise to the solution. After the addition of the (3-bromophenyl)methanol, the mixture was warmed to room temperature and stirred for 2 h. 5% HCl was added to the reaction mixture to adjust the pH=4-5. Then the organic phase was separated and the aqueous layer was extracted with CH2Cl2 (50 mL×2). The combined organic phases were washed with water and dried over Na2SO4. After removing the solvent, 28.5 g of {[(3-bromophenyl)methyl]oxy}(1,1-dimethylethyl)dimethylsilane was obtained (Yield: 95.1%). was added dropwise to the solution Then the organic phase was separated the aqueous layer was extracted with CH2Cl2 (50 mL×2) The combined organic phases were washed with water dried over Na2SO4 After removing the solvent

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

Procedure: TBSCl (18.7 g, 124.3 mmol), Et3N (14.08 g, 139.2 mmol) and DMAP (194.3 mg, 8.9 mmol) were dissolved in CH2Cl2 (120 mL), then the solution was cooled to 0-5° C. (3-bromophenyl)methanol (18.5 g, 99.4 mmol) was added dropwise to the solution. After the addition, the mixture was warmed to room temperature, and stirred for 2 h. 5% HCl was added to the reaction mixture to pH=4-5, then the organic phase was separated, and the aqueous layer was extracted with CH2Cl2 (50 mL×2). The combined organic phase was washed with water, and dried over Na2SO4. After removing the solvent, 28.5 g of {[(3-Bromophenyl)methyl]oxy}(1,1-dimethylethyl)dimethylsilane was obtained (Yield: 95.1%). was added dropwise to the solution After the addition the organic phase was separated the aqueous layer was extracted with CH2Cl2 (50 mL×2) The combined organic phase was washed with water dried over Na2SO4 After removing the solvent

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

Procedure: TBSCl (18.7 g, 124.3 mmol), Et3N (14.08 g, 139.2 mmol) and DMAP (194.3 mg, 8.9 mmol) were dissolved in CH2Cl2 (120 mL), then the solution was cooled to 0-5° C. (3-bromophenyl)methanol (18.5 g, 99.4 mmol) was added dropwise to the solution. After the addition, the mixture was warmed to room temperature, and stirred for 2 h. 5% HCl was added to the reaction mixture to pH=4-5, then the organic phase was separated, and the aqueous layer was extracted with CH2Cl2 (50 mL×2). The combined organic phase was washed with water, and dried over Na2SO4. After removing the solvent, 28.5 g of {[(3-Bromophenyl)methyl]oxy}(1,1-dimethylethyl)dimethylsilane was obtained (Yield: 95.1%). was added dropwise to the solution After the addition the organic phase was separated the aqueous layer was extracted with CH2Cl2 (50 mL×2) The combined organic phase was washed with water dried over Na2SO4 After removing the solvent

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of (3-bromobenzyloxy)(tert-butyl)dimethylsilane (16.72 g), isopropenyl acetate (9.2 mL), tri-n-butyltin methoxide (24 mL), palladium(II)acetate (0.625 g) and tri(o-tolyl)phosphine (1.70 g) in anhydrous toluene (65 mL) was heated at reflux at 100° C. for 5 hours and then left to cool overnight. The mixture was diluted with ethyl acetate (130 mL) and 4 molar aqueous potassium fluoride (80 mL) and stirred vigorously for 20 minutes. Diatomaceous earth was added and the suspension was then filtered through diatomaceous earth, washing the residue well with ethyl acetate. The combined filtrate and washings were dried over anhydrous magnesium sulphate and concentrated in vacuo and purified by flash chromatography on silica eluting with isohexane, 10% dichloromethane in isohexane and 20% diethyl ether in isohexane to afford the subtitled compound as a yellow oil. Yield 13.71 g. was heated left to cool overnight Diatomaceous earth was added the suspension was then filtered through diatomaceous earth washing the residue well with ethyl acetate The combined filtrate and washings were dried over anhydrous magnesium sulphate concentrated in vacuo purified by flash chromatography on silica eluting with isohexane, 10% dichloromethane in isohexane and 20% diethyl ether in isohexane