N,N-dimethylmethanamine oxide;dihydrate

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

Procedure: To a mixed solution of 0.17 g of tert-butyl (5-(bromomethyl)pyrazin-2-yl)carbamate in 4 mL of dimethyl sulfoxide and 2 mL of dichloromethane, 0.26 g of trimethylamine N-oxide dihydrate was added under cooling with ice, and the mixture was stirred for 2 hours. Thereto were added water and chloroform, the organic layer was separated, and washed with a saturated aqueous sodium hydrogen carbonate solution, water and a saturated aqueous sodium chloride solution. The organic layer was dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure to obtain 0.10 g of tert-butyl (5-formylpyrazin-2-yl)carbamate as a white solid. under cooling with ice the organic layer was separated washed with a saturated aqueous sodium hydrogen carbonate solution, water The organic layer was dried over anhydrous magnesium sulfate the solvent was distilled off under reduced pressure

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

Procedure: 3-Aza-tricyclo[7.2.1.02,7]dodeca-2(7),3,5,10-tetraene (960 mg, 6.1 mmol) and trimethylamine N-oxide dihydrate (748 mg, 6.73 mmol) were stirred in dichloromethane (15 mL) and treated with osmium tetroxide (OsO4, 0.2 mL of a 15 mol % t-butanol solution) and the mixture was stirred vigorously. After 18 h, the residue was poured onto a silica gel column (2×6 inch) and eluted with hexanes (100 mL) then EtOAc to elute product as an oil that crystallizes on standing (1.16 g, 100%). (TLC EtOAc Rf 0.17); 1H NMR (400 MHz, CDCl3) δ 8.12 (d, J=4.9 Hz, 1H), 7.40 (d, J=7.5 Hz, 1H), 7.07 (dd, J=7.5, 4.9 Hz, 1H), 4.19 (d, J=6.0 Hz, 1H), 3.90 (d, J=6.0 Hz, 1H), 3.45 (s, 1H), 3.00 (dd, J=17.3, 4.8 Hz, 1H), 2.67 (d, J=17.3 Hz, 1H), 2.43 (m, 2H), 1.59 (d, J=11.6 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 159.4, 147.6, 138.1, 130.9, 122.3, 77.1, 75.4, 51.6, 42.2, 33.9, 28.5; APCl MS m/z 192.1 (M)+. the residue was poured onto a silica gel column (2×6 inch) eluted with hexanes (100 mL) EtOAc to elute product as an oil that crystallizes

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

Procedure: 3-Aza-tricyclo[7.2.1.02,7]dodeca-2(7),3,5,10-tetraene (960 mg, 6.1 mmol) and trimethylamine N-oxide dihydrate (748 mg, 6.73 mmol) were stirred in dichloromethane (15 mL) and treated with osmium tetroxide (OsO4, 0.2 mL of a 15 mol % t-butanol solution) and the mixture was stirred vigorously. After 18 h, the residue was poured onto a silica gel column (2×6 inch) and eluted with hexanes (100 mL) then EtOAc to elute product as an oil that crystallizes on standing (1.16 g, 100%). (TLC EtOAc Rf 0.17); 1H NMR (400 MHz, CDCl3) δ 8.12 (d, J=4.9 Hz, 1H), 7.40 (d, J=7.5 Hz, 1H), 7.07 (dd, J=7.5, 4.9 Hz, 1H), 4.19 (d, J=6.0 Hz, 1H), 3.90 (d, J=6.0 Hz, 1H), 3.45 (s, 1H), 3.00 (dd, J=17.3, 4.8 Hz, 1H), 2.67 (d, J=17.3 Hz, 1H), 2.43 (m, 2H), 1.59 (d, J=11.6 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 159.4, 147.6, 138.1, 130.9, 122.3, 77.1, 75.4, 51.6, 42.2, 33.9, 28.5; APCl MS m/z 192.1 (M)+. the residue was poured onto a silica gel column (2×6 inch) eluted with hexanes (100 mL) EtOAc to elute product as an oil that crystallizes

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

Procedure: 9-BBN (3.0 mmol, 6 mL of a 0.5 M solution in hexanes) was added to a stirred solution of ethyl(2S)-2-ethoxy-3-(4-vinylphenyl)propanoate (0.37 g, 1.48 mmol) in dry THF under argon. The reaction mixture was stirred for 22 h under argon. Trimethylamine N-oxide dihydrate (0.60 g, 5.4 mmol) was added and the mixture was heated to reflux overnight and diluted with ether (50 mL). The organic layer was washed with brine (×3), dried (MgSO4), filtered, and evaporated. The crude product was purified by flash chromatography (silica, heptane/ethyl acetate 3:1) to give the title compound as an colorless oil (0.24 g, 62%). the mixture was heated to reflux overnight The organic layer was washed with brine (×3) dried (MgSO4) filtered evaporated The crude product was purified by flash chromatography (silica, heptane/ethyl acetate 3:1)

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

Procedure: 9-BBN (3.0 mmol, 6 mL of a 0.5 M solution in hexanes) was added to a stirred solution of ethyl(2S)-2-ethoxy-3-(4-vinylphenyl)propanoate (0.37 g, 1.48 mmol) in dry THF under argon. The reaction mixture was stirred for 22 h under argon. Trimethylamine N-oxide dihydrate (0.60 g, 5.4 mmol) was added and the mixture was heated to reflux overnight and diluted with ether (50 mL). The organic layer was washed with brine (×3), dried (MgSO4), filtered, and evaporated. The crude product was purified by flash chromatography (silica, heptane/ethyl acetate 3:1) to give the title compound as an colorless oil (0.24 g, 62%). the mixture was heated to reflux overnight The organic layer was washed with brine (×3) dried (MgSO4) filtered evaporated The crude product was purified by flash chromatography (silica, heptane/ethyl acetate 3:1)

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

Procedure: To 5-methylidene-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine (0.60 g) are added successively t-butyl alcohol (6.0 ml), water (1.2 ml), pyridine (0.3 ml), osmium tetroxide (1.2 mg) and trimethylamine N-oxide dihydrate (0.22 g), and the mixture is refluxed with stirring for 2.5 hours. After cooling, to the reaction solution is added 20% aqueous sodium hydrogensulfite solution (10 ml), and the mixture is stirred at room temperature for 1.5 hour. The reaction solution is extracted with a mixture of ethyl acetate/tetrahydrofuran (1:1). The extract is washed successively with diluted hydrochloric acid and saturated saline solution, and dried over magnesium sulfate. The solvent is distilled off and the resulting residue is recrystallized from ethyl acetate/n-hexane to give 5-hydroxymethyl-5-hydroxy-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine (0.55 g) as white powder, m.p. 136°-140° C. the mixture is refluxed After cooling, to the reaction solution the mixture is stirred at room temperature for 1.5 hour The reaction solution is extracted with a mixture of ethyl acetate/tetrahydrofuran (1:1) The extract is washed successively with diluted hydrochloric acid and saturated saline solution dried over magnesium sulfate The solvent is distilled off the resulting residue is recrystallized from ethyl acetate/n-hexane

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

Procedure: To a mixture of trimethylamine-N-oxide dihydrate (408 mg, 3.67 mmol) and spiro[cyclopent-3-ene-1,3′-pyrrolo[2,3-b]pyridin]-2′(1′H)-one (622 mg, 3.34 mmol) in dichloromethane (115 mL) was added osmium tetroxide (25 uL of 2.5% solution in 2-methyl-2-propanol). After 24 h the reaction mixture was concentrated. The crude product was loaded onto a silica gel chromatography column with a minimal amount of methanol and eluted with a gradient of 5 to 20% methanol:dichloromethane to give the title compound (0.63 g). MS: m/z=221.0 (M+1). After 24 h the reaction mixture was concentrated eluted with a gradient of 5 to 20% methanol

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

Procedure: To a mixed solution of 0.17 g of tert-butyl (5-(bromomethyl)pyrazin-2-yl)carbamate in 4 mL of dimethyl sulfoxide and 2 mL of dichloromethane, 0.26 g of trimethylamine N-oxide dihydrate was added under cooling with ice, and the mixture was stirred for 2 hours. Thereto were added water and chloroform, the organic layer was separated, and washed with a saturated aqueous sodium hydrogen carbonate solution, water and a saturated aqueous sodium chloride solution. The organic layer was dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure to obtain 0.10 g of tert-butyl (5-formylpyrazin-2-yl)carbamate as a white solid. under cooling with ice the organic layer was separated washed with a saturated aqueous sodium hydrogen carbonate solution, water The organic layer was dried over anhydrous magnesium sulfate the solvent was distilled off under reduced pressure

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

Procedure: 3-Aza-tricyclo[7.2.1.02,7]dodeca-2(7),3,5,10-tetraene (960 mg, 6.1 mmol) and trimethylamine N-oxide dihydrate (748 mg, 6.73 mmol) were stirred in dichloromethane (15 mL) and treated with osmium tetroxide (OsO4, 0.2 mL of a 15 mol % t-butanol solution) and the mixture was stirred vigorously. After 18 h, the residue was poured onto a silica gel column (2×6 inch) and eluted with hexanes (100 mL) then EtOAc to elute product as an oil that crystallizes on standing (1.16 g, 100%). (TLC EtOAc Rf 0.17); 1H NMR (400 MHz, CDCl3) δ 8.12 (d, J=4.9 Hz, 1H), 7.40 (d, J=7.5 Hz, 1H), 7.07 (dd, J=7.5, 4.9 Hz, 1H), 4.19 (d, J=6.0 Hz, 1H), 3.90 (d, J=6.0 Hz, 1H), 3.45 (s, 1H), 3.00 (dd, J=17.3, 4.8 Hz, 1H), 2.67 (d, J=17.3 Hz, 1H), 2.43 (m, 2H), 1.59 (d, J=11.6 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 159.4, 147.6, 138.1, 130.9, 122.3, 77.1, 75.4, 51.6, 42.2, 33.9, 28.5; APCl MS m/z 192.1 (M)+. the residue was poured onto a silica gel column (2×6 inch) eluted with hexanes (100 mL) EtOAc to elute product as an oil that crystallizes

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

Procedure: 253.3 g of hydrocarbon mixture containing about 60% of 2,2,5,5,8-pentamethyl-bicyclo[4.4.0]deca-1(6),8-diene are dissolved in 1050 ml of tert.butanol and treated with a solution of 91.65 g of trimethylamine N-oxide dihydrate in 375 ml of water. Thereto there is added a solution of 40 mg of osmium tetroxide in 75 ml of tert.butanol and the mixture is held for 48 hours at 95° C. with good stirring at reflux temperature. The solution is extracted with 2 l of dichloromethane, 1 l of water and 412.5 ml of 2N hydrochloric acid and ice. The organic phase is washed neutral twice with 1 l of water each time and the aqueous phases are extracted with dichloromethane. After drying over magnesium sulphate and concentration on a rotary evaporator, there are obtained 269 g of crude crystals. These are recrystallized from 150 ml of hexane and 80 ml of dichloromethane. There are obtained 167.0 g of crystalline 2,2,5,5,8-pentamethyl-bicyclo[4.4.0]dec-1(6)-ene-8,9-diol of melting point 98°-99.5° C. at reflux temperature The solution is extracted with 2 l of dichloromethane, 1 l of water and 412.5 ml of 2N hydrochloric acid and ice The organic phase is washed neutral twice with 1 l of water each time the aqueous phases are extracted with dichloromethane After drying over magnesium sulphate and concentration on a rotary evaporator, there are obtained 269 g of crude crystals These are recrystallized from 150 ml of hexane and 80 ml of dichloromethane

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

Procedure: Borane-tetrahydrofuran complex (1.0M in THF, 20 ml, 20 mmol) was added dropwise to an ice cooled solution of 1-acetyl-2,3-dihydro-5-ethenyl-1H-indole (5.61 g, 30 mmol) in TEF (150 ml). The mixture was stirred at 0° C. for 30 minute then at room temperature for 1 hr. Trimethylamine N-oxide dihydrate (8.88 g, 80 mmol) was added and the mixture was heated under reflux for 3 hr, cooled and poured into water (400 ml) and aqueous HCl (6N, 10 ml). The mixture was extracted with dichloromethane (3×400 ml) and the combined organic fractions were dried (Na2SO4) and evaporated under reduced pressure. The residue was purified by flash column chromatography on silica gel, eluting with ethyl acetate, to give the alcohol as a white solid (3.41 g, 55%). at room temperature for 1 hr the mixture was heated under reflux for 3 hr cooled The mixture was extracted with dichloromethane (3×400 ml) the combined organic fractions were dried (Na2SO4) evaporated under reduced pressure The residue was purified by flash column chromatography on silica gel eluting with ethyl acetate

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

Procedure: A slurry of tricyclo[5.2.1.02,6]deca-3,8-diene (26.5 g, 0.2 mol), trimethylamine N-oxide dihydrate (22.3 g, 0.2 mol) and osmium tetroxide (2.5 wt % solution in 2-methyl-2-propanol, 2 □l) in dichloromethane (200 ml) was stirred for 18 h. A further portion of osmium tetroxide (2.5 wt % solution in 2-methyl-2-propanol, ca. 2 □l) was added, water (25 ml) and acetone (50 ml) was added and the reaction mixture was stirred for a further 72 h. Pyridine (0.5 ml) and tetrabutylammonium acetate (0.5 g) were added. Florisil (10 g) and aqueous sodium hydrogensulfite solution was added and the reaction mixture was stirred for 20 min. The reaction mixture was filtered and the product was extracted with dichloromethane (3 times). The combined organic extracts were washed with water, brine and then concentrated to give an oil. The crude oil was purified by flash chromatography eluting with ethyl acetate:hexane (10:90) and then ethyl acetate, to give a waxy solid (6.5 g, 19%). the reaction mixture was stirred for 20 min The reaction mixture was filtered the product was extracted with dichloromethane (3 times) The combined organic extracts were washed with water, brine concentrated to give an oil The crude oil was purified by flash chromatography eluting with ethyl acetate:hexane (10:90)