1-fluoropropan-2-one

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

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

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

Procedure: Fluoroacetone (5 g) and 5,6-dichloro-2-amino-1-(2,3,5-tri-O-acetyl-beta-L-ribofuranosyl)-1H-benzimidazole (0.38 g, 0.82 mmol) were combined with tosic acid (0.050 g, 0.26 mmol) and stirred at reflux in a flask fitted with a Dean Stark trap. After four hours sodium cyanoborohydride (0.16 g, 2.4 mmol) was added and reflux was continued for six hours. The solution was diluted with ethyl acetate (200 mL) and washed with sat'd NaCl (2×50 mL) and water (50 mL). The organics were dried (Na2SO4), decanted, and concentrated. The crude product was purified on a silica gel column (230-400 mesh, 2.5×18 cm) with 1:25 methanol:CH2Cl2 gave 0.19 g of crude product This material was further purified on a chromatotron (2 mm rotor) with 1:1 ethyl acetate hexanes to give a light yellow solid (0.10 g, 0.20 mmol, 24%); MS (API+; m/z (rel. intensity) 520 (62.63, M+); 1H NMR (DMSO-d6) d 7.66 (s, 1H, Ar—H), 7.51 (s, 1H, Ar—H), 7.30 (d, 1 H, NH, J=7.6 Hz), 6.25 (d, 1H, H-1′, J=7.5 Hz), 5.31-5.23 (m, 1H, H-2′), 5.48-5.44 (m, 1H, H-3′), 4.63-4.26 (m, 6H, 2F, CH, H-4′ and 5′), 2.21 (s, 3H, OAc), 2.19 (s, 3H, OAc), 2.02 (s,3H, OAc), 1.24 (d, 3H, CH(CH3), J=7.5 Hz). at reflux in a flask fitted with a Dean Stark trap reflux washed with sat'd NaCl (2×50 mL) and water (50 mL) The organics were dried (Na2SO4) decanted concentrated The crude product was purified on a silica gel column (230-400 mesh, 2.5×18 cm) with 1:25 methanol CH2Cl2 gave 0.19 g of crude product This material was further purified on a chromatotron (2 mm rotor) with 1:1 ethyl acetate hexanes

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

Procedure: Trimethylsilyl cyanide (0.146 ml, 1.1 mmol) was added dropwise to the mixture of p-toluidine (0.107 g, 1 mmol) and fluoroacetone (0.082 g, 1.1 mmol). The reaction mixture was stirred at room temperature for 12 h and then concentrated under vacuum to obtain a brown liquid which was subjected to chromatography (dichloromethane) to yield 19a (0.179 g, 0.93 mmol, 93%) as a yellowish solid. concentrated under vacuum to obtain a brown liquid which

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

Procedure: Trimethylsilyl cyanide (0.146 ml, 1.1 mmol) was added dropwise to the mixture of p-toluidine (0.107 g, 1 mmol) and fluoroacetone (0.082 g, 1.1 mmol). The reaction mixture was stirred at room temperature for 12 h and then concentrated under vacuum to obtain a brown liquid which was subjected to chromatography (dichloromethane) to yield 19a (0.179 g, 0.93 mmol, 93%) as a yellowish solid. concentrated under vacuum to obtain a brown liquid which

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

Procedure: This compound was prepared according to a procedure similar to that described in Procedure B. A stirred solution of triethyl(ethynyl)silane (1.05 eq, 5.4 mL) in THF. at −78° C. was treated with n-BuLi (2.5 mol/L in hexanes, 1.1 eq) dropwise. The reaction was stirred for 15 minutes before addition of 1-fluoropropan-2-one (2.1 mL) then stirred for another hour at −78° C. whereupon it was slowly warmed to room temperature. The reaction was quenched with a saturated ammonium chloride solution then extracted with ethyl acetate. The organic layer was dried with magnesium sulfate, filtered and concentrated to give a clear oil. This crude intermediate was purified by ISCO with ELSD option (0-100% Heptane: Ethyl acetate over 25 minutes) to afford 1-fluoro-2-methyl-4-triethylsilyl-but-3-yn-2-ol. 1H NMR (400 MHz, MeOD) δ 4.81 (s, 1H), 4.36-4.27 (m, 1H), 4.24-4.14 (m, 1H), 1.45 (d, J=1.8 Hz, 3H), 1.06-0.97 (m, 9H), 0.65-0.55 (m, 6H). This compound was prepared was slowly warmed to room temperature The reaction was quenched with a saturated ammonium chloride solution then extracted with ethyl acetate The organic layer was dried with magnesium sulfate filtered concentrated to give a clear oil This crude intermediate was purified by ISCO with ELSD option (0-100% Heptane: Ethyl acetate over 25 minutes)

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

Procedure: This compound was prepared according to a procedure similar to that described in Procedure B. A stirred solution of triethyl(ethynyl)silane (1.05 eq, 5.4 mL) in THF. at −78° C. was treated with n-BuLi (2.5 mol/L in hexanes, 1.1 eq) dropwise. The reaction was stirred for 15 minutes before addition of 1-fluoropropan-2-one (2.1 mL) then stirred for another hour at −78° C. whereupon it was slowly warmed to room temperature. The reaction was quenched with a saturated ammonium chloride solution then extracted with ethyl acetate. The organic layer was dried with magnesium sulfate, filtered and concentrated to give a clear oil. This crude intermediate was purified by ISCO with ELSD option (0-100% Heptane: Ethyl acetate over 25 minutes) to afford 1-fluoro-2-methyl-4-triethylsilyl-but-3-yn-2-ol. 1H NMR (400 MHz, MeOD) δ 4.81 (s, 1H), 4.36-4.27 (m, 1H), 4.24-4.14 (m, 1H), 1.45 (d, J=1.8 Hz, 3H), 1.06-0.97 (m, 9H), 0.65-0.55 (m, 6H). This compound was prepared was slowly warmed to room temperature The reaction was quenched with a saturated ammonium chloride solution then extracted with ethyl acetate The organic layer was dried with magnesium sulfate filtered concentrated to give a clear oil This crude intermediate was purified by ISCO with ELSD option (0-100% Heptane: Ethyl acetate over 25 minutes)

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

Procedure: Fluoroacetone (5 g) and 5,6-dichloro-2-amino-1-(2,3,5-tri-O-acetyl-beta-L-ribofuranosyl)-1H-benzimidazole (0.38 g, 0.82 mmol) were combined with tosic acid (0.050 g, 0.26 mmol) and stirred at reflux in a flask fitted with a Dean Stark trap. After four hours sodium cyanoborohydride (0.16 g, 2.4 mmol) was added and reflux was continued for six hours. The solution was diluted with ethyl acetate (200 mL) and washed with sat'd NaCl (2×50 mL) and water (50 mL). The organics were dried (Na2SO4), decanted, and concentrated. The crude product was purified on a silica gel column (230-400 mesh, 2.5×18 cm) with 1:25 methanol:CH2Cl2 gave 0.19 g of crude product This material was further purified on a chromatotron (2 mm rotor) with 1:1 ethyl acetate hexanes to give a light yellow solid (0.10 g, 0.20 mmol, 24%); MS (API+; m/z (rel. intensity) 520 (62.63, M+); 1H NMR (DMSO-d6) d 7.66 (s, 1H, Ar—H), 7.51 (s, 1H, Ar—H), 7.30 (d, 1 H, NH, J=7.6 Hz), 6.25 (d, 1H, H-1′, J=7.5 Hz), 5.31-5.23 (m, 1H, H-2′), 5.48-5.44 (m, 1H, H-3′), 4.63-4.26 (m, 6H, 2F, CH, H-4′ and 5′), 2.21 (s, 3H, OAc), 2.19 (s, 3H, OAc), 2.02 (s,3H, OAc), 1.24 (d, 3H, CH(CH3), J=7.5 Hz). at reflux in a flask fitted with a Dean Stark trap reflux washed with sat'd NaCl (2×50 mL) and water (50 mL) The organics were dried (Na2SO4) decanted concentrated The crude product was purified on a silica gel column (230-400 mesh, 2.5×18 cm) with 1:25 methanol CH2Cl2 gave 0.19 g of crude product This material was further purified on a chromatotron (2 mm rotor) with 1:1 ethyl acetate hexanes

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

Procedure: Fluoroacetone (5 g) and 5,6-dichloro-2-amino-1-(2,3,5-tri-O-acetyl-beta-L-ribofuranosyl)-1H-benzimidazole (0.38 g, 0.82 mmol) were combined with tosic acid (0.050 g, 0.26 mmol) and stirred at reflux in a flask fitted with a Dean Stark trap. After four hours sodium cyanoborohydride (0.16 g, 2.4 mmol) was added and reflux was continued for six hours. The solution was diluted with ethyl acetate (200 mL) and washed with sat'd NaCl (2×50 mL) and water (50 mL). The organics were dried (Na2SO4), decanted, and concentrated. The crude product was purified on a silica gel column (230-400 mesh, 2.5×18 cm) with 1:25 methanol:CH2Cl2 gave 0.19 g of crude product This material was further purified on a chromatotron (2 mm rotor) with 1:1 ethyl acetate hexanes to give a light yellow solid (0.10 g, 0.20 mmol, 24%); MS (API+; m/z (rel. intensity) 520 (62.63, M+); 1H NMR (DMSO-d6) d 7.66 (s, 1H, Ar—H), 7.51 (s, 1H, Ar—H), 7.30 (d, 1 H, NH, J=7.6 Hz), 6.25 (d, 1H, H-1′, J=7.5 Hz), 5.31-5.23 (m, 1H, H-2′), 5.48-5.44 (m, 1H, H-3′), 4.63-4.26 (m, 6H, 2F, CH, H-4′ and 5′), 2.21 (s, 3H, OAc), 2.19 (s, 3H, OAc), 2.02 (s,3H, OAc), 1.24 (d, 3H, CH(CH3), J=7.5 Hz). at reflux in a flask fitted with a Dean Stark trap reflux washed with sat'd NaCl (2×50 mL) and water (50 mL) The organics were dried (Na2SO4) decanted concentrated The crude product was purified on a silica gel column (230-400 mesh, 2.5×18 cm) with 1:25 methanol CH2Cl2 gave 0.19 g of crude product This material was further purified on a chromatotron (2 mm rotor) with 1:1 ethyl acetate hexanes

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

Procedure: Trimethylsilyl cyanide (0.146 ml, 1.1 mmol) was added dropwise to the mixture of p-toluidine (0.107 g, 1 mmol) and fluoroacetone (0.082 g, 1.1 mmol). The reaction mixture was stirred at room temperature for 12 h and then concentrated under vacuum to obtain a brown liquid which was subjected to chromatography (dichloromethane) to yield 19a (0.179 g, 0.93 mmol, 93%) as a yellowish solid. concentrated under vacuum to obtain a brown liquid which

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

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