Sodium;3-oxidodioxaborirane;tetrahydrate

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 5-formyl-2-{[(1R)-1-methylpropyl]oxy}benzonitrile (D37) (310 mg, 1.53 mmol) in acetic acid (30 ml) was added sodium perborate tetrahydrate (471 mg, 3.05 mmol), the reaction mixture was heated at 50° C. over the weekend. The reaction mixture was concentrated in vacuo and water (˜50 ml) added, EtOAc (˜30 ml) was added and the layers partitioned, the aq layer was extracted twice more with EtOAc (˜30 ml) and the combined organics evaporated to dryness under reduced pressure to give the title compound (315 mg) as an off-white solid. δH (d6-DMSO, 400 MHz): 8.07-8.24 (2H, m), 7.38 (1H, d), 4.63-4.77 (1H, m), 1.55-1.83 (2H, m), 1.31 (3H, d), 0.95 (3H, t). MS (ES+): C12H13NO2 requires 219; found 220 (MH+). The reaction mixture was concentrated in vacuo and water (˜50 ml) added EtOAc (˜30 ml) was added the layers partitioned the aq layer was extracted twice more with EtOAc (˜30 ml) the combined organics evaporated to dryness under reduced pressure

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 5-formyl-2-{[(1S)-1-methylpropyl]oxy}benzonitrile (D35) (220 mg, 1.08 mmol) in acetic acid (20 ml) was added sodium perborate tetrahydrate (334 mg, 2.17 mmol), the reaction mixture was heated at 50° C. over the weekend. The reaction mixture was concentrated in-vacuo. Water (˜50 ml) was added, EtOAc (˜30 ml) was added and the layers partitioned, the aq layer was extracted twice more with EtOAc (˜30 ml) and the combined organics were evaporated to dryness under reduced pressure to give the title compound (245 mg) as an off white solid. δH (d6-DMSO, 400 MHz): 8.17 (2H, apparent d), 7.39 (1H, s), 4.68-4.74 (1H, m), 1.55-1.76 (2H, m), 1.31 (3H, d), 0.95 (3H, t). MS (ES): C12H13NO2 requires 219; found 220 (MH+). The reaction mixture was concentrated in-vacuo Water (˜50 ml) was added EtOAc (˜30 ml) was added the layers partitioned the aq layer was extracted twice more with EtOAc (˜30 ml) the combined organics were evaporated to dryness under reduced pressure

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

Procedure: Borane-methyl sulfide complex (2 M in ether, 11 mL, 22 mmol) was added dropwise to a cooled (−5° C.) solution of 4-[1-(3,4-dimethoxyphenoxy)-3-butenyl]benzonitrile (see step (i) above; 17.6 g, 56.8 mmol) in dry THF (15 mL) over a period of 15 minutes (during which time the reaction temperature rose to 0° C.). The resulting mixture was stirred at between 0 and 10° C. for 1.5 h, before being allowed to warm to rt. Stirring was continued for a further 3.5 h at this temperature before water (22 mL) and sodium perborate tetrahydrate (11 g, 66 mmol) were added. The biphasic mixture was stirred for 2 h at rt before the water layer was separated and extracted with ether. The combined organic layers were washed with brine, dried and concentrated in vacuo. The resulting residue was purified by chromatography on silica gel, eluting with IPA: ethyl acetate:heptane (5:25:70) to yield 14.5 g (77%) of the sub-title compound. rose to 0° C. Stirring were added was separated extracted with ether The combined organic layers were washed with brine dried concentrated in vacuo The resulting residue was purified by chromatography on silica gel eluting with IPA: ethyl acetate:heptane (5:25:70)

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

Procedure: Borane-methyl sulfide complex (2 M in ether, 11 mL, 22 mmol) was added dropwise to a cooled (−5° C.) solution of 4-[1-(3,4-dimethoxyphenoxy)-3-butenyl]benzonitrile (from step (i) above; 17.6 g, 56.8 mmol) in dry THF (15 mL) over a period of 15 minutes (during which time the reaction temperature rose to 0° C.). The resulting mixture was stirred at between 0 and 10° C. for 1.5 h, before being allowed to warm to rt. Stirring was continued for a further 3.5 h at this temperature before water (22 mL) and sodium perborate tetrahydrate (11 g, 66 mmol) were added. The biphasic mixture was stirred for 2 h at rt before the water layer was separated and extracted with ether. The combined organic layers were washed with brine, dried and concentrated in vacuo. The resulting residue was purified by chromatography on silica gel, eluting with IPA:ethyl acetate:heptane (5:25:70) to yield 14.5 g (77%) of the sub-title compound. rose to 0° C. Stirring were added was separated extracted with ether The combined organic layers were washed with brine dried concentrated in vacuo The resulting residue was purified by chromatography on silica gel eluting with IPA:ethyl acetate:heptane (5:25:70)

Conditions: temp:40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 5,6,7,8-tetrahydroquinoline-3-carbonitrile (633 mg, 4.00 mmol) in acetic acid (5 ml) at 40° C. was portionwise added sodium perborate tetrahydrate (677 mg, 4.4 mmol) and the mixture was stirred at 40° C. for 16 hours. The acetic acid was removed by evaporation under reduced pressure, the residue was basified with aqueous saturated NaHCO3 solution, the mixture extracted thrice with ethyl acetate, the combined extracts were dried over Na2SO4 and the solvent removed in vacuum to give the 3-cyano-5,6,7,8-tetrahydroquinoline 1-oxide (645 mg, 3.7 mmol, 92.5% yield) as a white solid. MS (ISP): m/z=175.1 [(M+H)+]. at 40° C. The acetic acid was removed by evaporation under reduced pressure the mixture extracted thrice with ethyl acetate the combined extracts were dried over Na2SO4 the solvent removed in vacuum

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

Procedure: To a stirring solution of 2-(methylthio)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidine (from step A) (1.167 g, 4.63 mmol) in THF/H2O (20 mL 1:1) at room temperature under argon was added sodium perborate tetrahydrate (2.137 g, 13.9 mmol). The reaction mixture was stirred at room temperature overnight. The reaction was cooled to room temperature. EtOAc (10 mL) was added to the reaction mixture, which was washed with brine (15 mL×3). Organic phase was dried (MgSO4), filtered and concentrated. The crude product was very insoluble, therefore it was used directly to next step. MS (ESI) 143 (M+H). The reaction was cooled to room temperature was washed with brine (15 mL×3) Organic phase was dried (MgSO4) filtered concentrated

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Trifluoroacetic acid (50 ml), acetic acid (50 ml) and sodium perborate tetrahydrate (26.6 g) were added to methyl 4-amino-2,5-difluoro-3-methylbenzoate (7.5 g), and the mixture was stirred at 60° C. for 24 hours. Impurities in the reaction mixture was removed by filtration, chloroform was added to the resultant filtrate, and the resultant mixture was washed with water. After an organic layer was dried over anhydrous magnesium sulfate, the solvent was distilled off under reduced pressure to obtain the title compound (6.1 g) as a reddish brown oil. Impurities in the reaction mixture was removed by filtration, chloroform was added to the resultant filtrate the resultant mixture was washed with water After an 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: Under the conditions of Example 3, 76 mg of 7α-{5-[(2S)-2-(4,4,5,5,5-pentafluoropentylthiomethyl)-pyrrolidin-1-yl]-pentyl}-estra-1,3,5(10)-triene-3,17β-diol (Example 26f) is acetylated with acetic anhydride, and the crude product is oxidized, as described in Example 4, with sodium perborate tetrahydrate, worked up and chromatographed. 31 mg of the title compound is obtained as oil. [α]D22 =30.6°(c=0.515 in methanol). chromatographed

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

Procedure: To a solution of the 4-cyclohex-1-en-1-yl-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazole (775 mg, 3.34 mmol) prepared in Example 33a in THF (4 mL), a borane-THF complex (0.95 M; 3.4 mL, 3.23 mmol) was added with cooling on ice, and the reaction solution was stirred for 30 minutes with cooling on ice. To the reaction solution, a borane-THF complex (0.95 M; 3.4 mL, 3.23 mmol) was added again, and the mixture was stirred at room temperature for 90 minutes. To the reaction solution, water (5 mL) and subsequently sodium perborate tetrahydrate (1.00 g, 6.50 mmol) were added, and the mixture was stirred for 5 hours. To the reaction solution, sodium thiosulfate (2.0 g) was added, followed by extraction with ethyl acetate (50 mL). The thus obtained organic layer was dried over anhydrous sodium sulfate. After vacuum concentration, the residue was purified with column chromatography (dichloromethane/methanol=97:3) to yield the title compound (590 mg, 71%) as a colorless oil. with cooling on ice with cooling on ice To the reaction solution, a borane-THF complex (0.95 M; 3.4 mL, 3.23 mmol) was added again the mixture was stirred at room temperature for 90 minutes the mixture was stirred for 5 hours followed by extraction with ethyl acetate (50 mL) The thus obtained organic layer was dried over anhydrous sodium sulfate After vacuum concentration the residue was purified with column chromatography (dichloromethane/methanol=97:3)

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

Procedure: Placed pyridin-2-yl(tetrahydro-2H-thiopyran-4-yl)methanol (1.560 g, 7.453 mmol) in glacial acetic acid (2 mL). Sodium perborate tetrahydrate (2.293 g, 14.91 mmol) was added and stirred for 18 hours. The reaction was partitioned between saturated sodium bisulfite and CH2Cl2. The solids were filtered off, washed with water and dried to afford the title compound (1.233 g, 68.56% yield) The reaction was partitioned between saturated sodium bisulfite and CH2Cl2 The solids were filtered off washed with water dried

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

Procedure: 4-(4-bromo-phenylsulfanyl)-piperidine-1-carboxylic acid benzyl ester (1.2 g, 2.96 mmol, 1 equiv) and sodium perborate tetrahydrate (NaBO3.4H2O) (1.36 g, 8.87 mmol, 3 equiv) were heated to 55° C. in HOAc and stirred for 18 h. The reaction was cooled to room temperature and poured onto water. The aqueous phase was extracted with EtOAc (3×100 mL). The organic phases were combined and washed carefully with saturated sodium bicarbonate solution (CAUTION: copious gas evolution), dried over sodium sulfate, filtered and evaporated to yield a white solid (1.2 g, 93% yield). Rf=0.16 (20% EtOAc/hexanes). poured onto water The aqueous phase was extracted with EtOAc (3×100 mL) washed carefully with saturated sodium bicarbonate solution (CAUTION: copious gas evolution) dried over sodium sulfate filtered evaporated

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

Procedure: 4-(4-bromo-phenylsulfanyl)-piperidine-1-carboxylic acid benzyl ester (1.2 g, 2.96 mmol, 1 equiv) and sodium perborate tetrahydrate (NaBO3.4H2O) (1.36 g, 8.87 mmol, 3 equiv) were heated to 55° C. in HOAc and stirred for 18 h. The reaction was cooled to room temperature and poured onto water. The aqueous phase was extracted with EtOAc (3×100 mL). The organic phases were combined and washed carefully with saturated sodium bicarbonate solution (CAUTION: copious gas evolution), dried over sodium sulfate, filtered and evaporated to yield a white solid (1.2 g, 93% yield). Rf=0.16 (20% EtOAc/hexanes). poured onto water The aqueous phase was extracted with EtOAc (3×100 mL) washed carefully with saturated sodium bicarbonate solution (CAUTION: copious gas evolution) dried over sodium sulfate filtered evaporated