(3S,3aR,6R,6aS)-6-[tert-butyl(dimethyl)silyl]oxy-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-3-ol

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

Procedure: Triphenylphosphine (34.1 mg, 0.130 mmol) and DEAD (0.021 ml, 0.130 mmol) were added to a stirred mixture of 5-([1,1′-biphenyl]-4-yl)-6-chloro-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazo[4,5-b]pyridine-2-thiol (30.4 mg, 0.065 mmol) and (3S,3aR,6R,6aS)-6-((tert-butyldimethylsilyl)oxy)hexahydrofuro[3,2-b]furan-3-ol (25.4 mg, 0.097 mmol) in THF (1 ml) and the mixture was stirred at room temperature overnight. The reaction mixture was concentrated under reduced pressure and the resulting residue was purified by preparative TLC, eluting with EtOAc/isohexane (2:8) to give the title compound. LC-MS: calculated for C36H48ClN3O4SSi2 709.26 observed m/e: 710.42 (M+H)+ (Rt 1.59/2 min); The reaction mixture was concentrated under reduced pressure the resulting residue was purified by preparative TLC eluting with EtOAc/isohexane (2:8)

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

Procedure: Triphenylphosphine (34.1 mg, 0.130 mmol) and DEAD (0.021 ml, 0.130 mmol) were added to a stirred mixture of 5-([1,1′-biphenyl]-4-yl)-6-chloro-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazo[4,5-b]pyridine-2-thiol (30.4 mg, 0.065 mmol) and (3S,3aR,6R,6aS)-6-((tert-butyldimethylsilyl)oxy)hexahydrofuro[3,2-b]furan-3-ol (25.4 mg, 0.097 mmol) in THF (1 ml) and the mixture was stirred at room temperature overnight. The reaction mixture was concentrated under reduced pressure and the resulting residue was purified by preparative TLC, eluting with EtOAc/isohexane (2:8) to give the title compound. LC-MS: calculated for C36H48ClN3O4SSi2 709.26 observed m/e: 710.42 (M+H)+ (Rt 1.59/2 min); The reaction mixture was concentrated under reduced pressure the resulting residue was purified by preparative TLC eluting with EtOAc/isohexane (2:8)

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

Procedure: To a stirred solution of triphenylphosphine (542 mg, 2.066 mmol), benzoic acid (252 mg, 2.066 mmol), and (3R,3aR,6R,6aS)-6-((tert-butyldimethylsilyl)oxy)hexahydrofuro[3,2-b]furan-3-ol (538 mg, 2.066 mmol) in anhydrous THF (8.0 mL) under nitrogen at room temperature was added DIAD (0.40 mL, 418 mg, 2.066 mmol), dropwise, over 10 min. After stirring for 16 h at room temperature, the mixture was concentrated under reduced pressure. The resultant residue was chromatographed using a Biotage™ 50 g (2×25 g in series) silica gel cartridge eluting with 0-50% EtOAc in 1:1 Hexane/DCM over 20 column volumes. The fractions containing desired product were combined and concentrated under reduced pressure. The resultant colorless oil was dissolved in MeOH (10 mL), and 5N aqueous NaOH (2.0 mL, 10.0 mmol) was added. After stirring for 20 h at room temperature, the mixture was poured into saturated aqueous sodium bicarbonate (100 mL) and extracted with ethyl acetate (2×100 mL). The combined organic layers were dried over sodium sulfate, and then concentrated under reduced pressure to afford the title compound as a white solid. LC-MS: calculated for C12H24O4Si 260.14, observed m/e: 261.17 (M+H)+ (Rt 0.42/4 min)1H NMR (500 MHz, CDCl3): δ 4.49 (t, J=4.5 Hz, 1H), 4.34 (d, J=4.3 Hz, 1H), 4.25 (m, 2H), 3.92 (dd, J=10.0, 3.5 Hz, 1H), 3.84 (d, J=10.0 Hz, 1H), 3.73 (dd, J=8.5, 6.0 Hz, 1H), 3.50 (t, J=8.0 Hz, 1H), 2.84 (s, 1H), 0.88 (s, 9H), 0.09 (s, 3H), 0.08 (s, 3H). the mixture was concentrated under reduced pressure The resultant residue was chromatographed eluting with 0-50% EtOAc in 1:1 Hexane/DCM over 20 column volumes The fractions containing desired product concentrated under reduced pressure The resultant colorless oil was dissolved in MeOH (10 mL) After stirring for 20 h at room temperature extracted with ethyl acetate (2×100 mL) The combined organic layers were dried over sodium sulfate concentrated under reduced pressure

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

Procedure: To a stirred solution of triphenylphosphine (542 mg, 2.066 mmol), benzoic acid (252 mg, 2.066 mmol), and (3R,3aR,6R,6aS)-6-((tert-butyldimethylsilyl)oxy)hexahydrofuro[3,2-b]furan-3-ol (538 mg, 2.066 mmol) in anhydrous THF (8.0 mL) under nitrogen at room temperature was added DIAD (0.40 mL, 418 mg, 2.066 mmol), dropwise, over 10 min. After stirring for 16 h at room temperature, the mixture was concentrated under reduced pressure. The resultant residue was chromatographed using a Biotage™ 50 g (2×25 g in series) silica gel cartridge eluting with 0-50% EtOAc in 1:1 Hexane/DCM over 20 column volumes. The fractions containing desired product were combined and concentrated under reduced pressure. The resultant colorless oil was dissolved in MeOH (10 mL), and 5N aqueous NaOH (2.0 mL, 10.0 mmol) was added. After stirring for 20 h at room temperature, the mixture was poured into saturated aqueous sodium bicarbonate (100 mL) and extracted with ethyl acetate (2×100 mL). The combined organic layers were dried over sodium sulfate, and then concentrated under reduced pressure to afford the title compound as a white solid. LC-MS: calculated for C12H24O4Si 260.14, observed m/e: 261.17 (M+H)+ (Rt 0.42/4 min)1H NMR (500 MHz, CDCl3): δ 4.49 (t, J=4.5 Hz, 1H), 4.34 (d, J=4.3 Hz, 1H), 4.25 (m, 2H), 3.92 (dd, J=10.0, 3.5 Hz, 1H), 3.84 (d, J=10.0 Hz, 1H), 3.73 (dd, J=8.5, 6.0 Hz, 1H), 3.50 (t, J=8.0 Hz, 1H), 2.84 (s, 1H), 0.88 (s, 9H), 0.09 (s, 3H), 0.08 (s, 3H). the mixture was concentrated under reduced pressure The resultant residue was chromatographed eluting with 0-50% EtOAc in 1:1 Hexane/DCM over 20 column volumes The fractions containing desired product concentrated under reduced pressure The resultant colorless oil was dissolved in MeOH (10 mL) After stirring for 20 h at room temperature extracted with ethyl acetate (2×100 mL) The combined organic layers were dried over sodium sulfate concentrated under reduced pressure

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

Procedure: Triphenylphosphine (34.1 mg, 0.130 mmol) and DEAD (0.021 ml, 0.130 mmol) were added to a stirred mixture of 5-([1,1′-biphenyl]-4-yl)-6-chloro-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazo[4,5-b]pyridine-2-thiol (30.4 mg, 0.065 mmol) and (3S,3aR,6R,6aS)-6-((tert-butyldimethylsilyl)oxy)hexahydrofuro[3,2-b]furan-3-ol (25.4 mg, 0.097 mmol) in THF (1 ml) and the mixture was stirred at room temperature overnight. The reaction mixture was concentrated under reduced pressure and the resulting residue was purified by preparative TLC, eluting with EtOAc/isohexane (2:8) to give the title compound. LC-MS: calculated for C36H48ClN3O4SSi2 709.26 observed m/e: 710.42 (M+H)+ (Rt 1.59/2 min); The reaction mixture was concentrated under reduced pressure the resulting residue was purified by preparative TLC eluting with EtOAc/isohexane (2:8)

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

Procedure: To a stirred solution of triphenylphosphine (542 mg, 2.066 mmol), benzoic acid (252 mg, 2.066 mmol), and (3R,3aR,6R,6aS)-6-((tert-butyldimethylsilyl)oxy)hexahydrofuro[3,2-b]furan-3-ol (538 mg, 2.066 mmol) in anhydrous THF (8.0 mL) under nitrogen at room temperature was added DIAD (0.40 mL, 418 mg, 2.066 mmol), dropwise, over 10 min. After stirring for 16 h at room temperature, the mixture was concentrated under reduced pressure. The resultant residue was chromatographed using a Biotage™ 50 g (2×25 g in series) silica gel cartridge eluting with 0-50% EtOAc in 1:1 Hexane/DCM over 20 column volumes. The fractions containing desired product were combined and concentrated under reduced pressure. The resultant colorless oil was dissolved in MeOH (10 mL), and 5N aqueous NaOH (2.0 mL, 10.0 mmol) was added. After stirring for 20 h at room temperature, the mixture was poured into saturated aqueous sodium bicarbonate (100 mL) and extracted with ethyl acetate (2×100 mL). The combined organic layers were dried over sodium sulfate, and then concentrated under reduced pressure to afford the title compound as a white solid. LC-MS: calculated for C12H24O4Si 260.14, observed m/e: 261.17 (M+H)+ (Rt 0.42/4 min)1H NMR (500 MHz, CDCl3): δ 4.49 (t, J=4.5 Hz, 1H), 4.34 (d, J=4.3 Hz, 1H), 4.25 (m, 2H), 3.92 (dd, J=10.0, 3.5 Hz, 1H), 3.84 (d, J=10.0 Hz, 1H), 3.73 (dd, J=8.5, 6.0 Hz, 1H), 3.50 (t, J=8.0 Hz, 1H), 2.84 (s, 1H), 0.88 (s, 9H), 0.09 (s, 3H), 0.08 (s, 3H). the mixture was concentrated under reduced pressure The resultant residue was chromatographed eluting with 0-50% EtOAc in 1:1 Hexane/DCM over 20 column volumes The fractions containing desired product concentrated under reduced pressure The resultant colorless oil was dissolved in MeOH (10 mL) After stirring for 20 h at room temperature extracted with ethyl acetate (2×100 mL) The combined organic layers were dried over sodium sulfate concentrated under reduced pressure