2-(4-fluorophenyl)ethanethiol

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: The title compound was prepared from 3-(4-carboxymethyl-phenyl)-2-chloro-propionic acid 2,2,2-trichloro-ethyl ester (1.17 g, 3.13 mmol) and 2-(4-fluoro-phenyl)-ethanethiol (0.53 g, 3.44 mmol) as described for 3-[4-(tert-butyl-dimethyl-silanyloxy-methyl)-phenyl]-2-[2-(4-fluoro-phenyl)-ethylsulfanyl]-propionic acid methyl ester. After purification by flash chromatography with n-heptane/EtOAc 10:1 as the eluent the product was obtained as a solid (611 mg, 39.6%). 1H NMR (300 MHz, CDCl3): δ 7.09-7.23 (m, 6H), 6.94-6.99 (m, 2H), 4.65-4.77 (q, 2H), 3.56-3.61 (m, 3H), 3.18-3.28 (dd, 1H), 2.78-3.02 (m, 5H). After purification by flash chromatography with n-heptane/EtOAc 10:1 as the eluent the product

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: The title compound was prepared from 2-chloro-3-[4-(3-hydroxy-propyl)-phenyl]-propionic acid 2,2,2-trichloro-ethyl ester (0.74 g, 1.98 mmol) and 2-(4-fluoro-phenyl)-ethanethiol (0.34 g, 2.17 mmol) as described for 3-[4-(tert-butyl-dimethyl-silanyloxy-methyl)-phenyl]-2-[2-(4-fluoro-phenyl)-ethylsulfanyl]-propionic acid methyl ester. After repeated purification by flash chromatography with n-heptane/EtOAc 9:1 as the eluent the product was obtained as an oil (94 mg, 9.6%). 1H NMR (300 MHz, CDCl3): δ 7.10-7.11 (m, 6H), 6.94-6.98 (t, 2H), 4.65-4.75 (q, 2H), 3.64-3.68 (t, 2H), 3.58-3.61 (dd, 2H), 3.17-3.23 (dd, 2H), 2.80-2.97 (m, 5H), 2.65-2.70 (t, 2H), 1.86-1.89 (m, 2H). purification by flash chromatography with n-heptane/EtOAc 9:1 as the eluent the product

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: The title compound was prepared from 2-chloro-3-[4-(3-hydroxy-propyl)-phenyl]-propionic acid 2,2,2-trichloro-ethyl ester (0.74 g, 1.98 mmol) and 2-(4-fluoro-phenyl)-ethanethiol (0.34 g, 2.17 mmol) as described for 3-[4-(tert-butyl-dimethyl-silanyloxy-methyl)-phenyl]-2-[2-(4-fluoro-phenyl)-ethylsulfanyl]-propionic acid methyl ester. After repeated purification by flash chromatography with n-heptane/EtOAc 9:1 as the eluent the product was obtained as an oil (94 mg, 9.6%). 1H NMR (300 MHz, CDCl3): δ 7.10-7.11 (m, 6H), 6.94-6.98 (t, 2H), 4.65-4.75 (q, 2H), 3.64-3.68 (t, 2H), 3.58-3.61 (dd, 2H), 3.17-3.23 (dd, 2H), 2.80-2.97 (m, 5H), 2.65-2.70 (t, 2H), 1.86-1.89 (m, 2H). purification by flash chromatography with n-heptane/EtOAc 9:1 as the eluent the product

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: The title compound was prepared from 2-chloro-3-[4-(2-hydroxy-ethyl)-phenyl]-propionic acid 2,2,2-trichloro-ethyl ester (2.57 g, 7.14 mmol) and 2-(4-fluoro-phenyl)-ethanethiol (1.23 g, 7.85 mmol) as described for 3-[4-(tert-butyl-dimethyl-silanyloxy-methyl)-phenyl]-2-[2-(4-fluoro-phenyl)-ethylsulfanyl]-propionic acid methyl ester. After purification by flash chromatography with n-heptane/EtOAc 5:1 as the eluent the product was obtained as an oil (1.0 g, 29.2%). 1H NMR (300 MHz, CDCl3): δ 7.10-7.14 (m, 6H), 6.93-6.99 (t, 2H), 4.65-4.76 (q, 2H), 3.82-3.86 (t, 2H), 3.55-3.60 (dd, 2H), 3.17-3.25 (dd, 2H), 2.81-3.00 (m, 7H). After purification by flash chromatography with n-heptane/EtOAc 5:1 as the eluent the product

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 3-[4-(tert-butyl-dimethyl-silanyloxymethyl)-phenyl]-2-chloro-propionic acid methyl ester (6.56 g, 42 mmol) in anhydrous DMF (200 mL) was added Cs2CO3 (14.34 g, 44 mmol) at 0° C. After stirring for 30 min 2-(4-fluoro-phenyl)-ethanethiol (13.72 g, 40 mmol), dissolved in anhydrous DMF (100 mL), was added dropwise and the resulting organe mixture was stirred for 18 h without removing the cooling bath. The mixture was diluted with Et2O and extracted with three times with H2O. The organic phase was concentrated under reduced pressure and the residue was dissolved in Et2O again and repeatedly extracted with H2O. After drying the separated organic layer over MgSO4, the solvent was removed under reduced pressure to afford the crude product as an orange oil which was purified by chromatography using n-heptane/EtOAc 20:1 as the eluent. The desired product was obtained as an oil (4.93 g, 25.4%). 1H NMR (400 MHz, CDCl3): δ 7.16 (d, 2H), 7.06-6.99 (m, 4H), 6.88 (t, 2H), 4.62 (s, 2H), 3.58 (s, 3H), 3.41 (dd, 1H), 3.10 (dd, 1H), 2.82 (dd, 1H), 2.74-2.76 (m, 4H), 0.85 (s, 9H), 0.00 (s, 6H). was added dropwise without removing the cooling bath The mixture was diluted with Et2O extracted with three times with H2O The organic phase was concentrated under reduced pressure the residue was dissolved in Et2O again repeatedly extracted with H2O After drying the separated organic layer over MgSO4 the solvent was removed under reduced pressure to afford the crude product as an orange oil which was purified by chromatography

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 3-[4-(tert-butyl-dimethyl-silanyloxymethyl)-phenyl]-2-chloro-propionic acid methyl ester (6.56 g, 42 mmol) in anhydrous DMF (200 mL) was added Cs2CO3 (14.34 g, 44 mmol) at 0° C. After stirring for 30 min 2-(4-fluoro-phenyl)-ethanethiol (13.72 g, 40 mmol), dissolved in anhydrous DMF (100 mL), was added dropwise and the resulting organe mixture was stirred for 18 h without removing the cooling bath. The mixture was diluted with Et2O and extracted with three times with H2O. The organic phase was concentrated under reduced pressure and the residue was dissolved in Et2O again and repeatedly extracted with H2O. After drying the separated organic layer over MgSO4, the solvent was removed under reduced pressure to afford the crude product as an orange oil which was purified by chromatography using n-heptane/EtOAc 20:1 as the eluent. The desired product was obtained as an oil (4.93 g, 25.4%). 1H NMR (400 MHz, CDCl3): δ 7.16 (d, 2H), 7.06-6.99 (m, 4H), 6.88 (t, 2H), 4.62 (s, 2H), 3.58 (s, 3H), 3.41 (dd, 1H), 3.10 (dd, 1H), 2.82 (dd, 1H), 2.74-2.76 (m, 4H), 0.85 (s, 9H), 0.00 (s, 6H). was added dropwise without removing the cooling bath The mixture was diluted with Et2O extracted with three times with H2O The organic phase was concentrated under reduced pressure the residue was dissolved in Et2O again repeatedly extracted with H2O After drying the separated organic layer over MgSO4 the solvent was removed under reduced pressure to afford the crude product as an orange oil which was purified by chromatography

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Thioacetic acid S-[2-(4-fluoro-phenyl)-ethyl]ester (9.9 g, 50 mmol) was dissolved in anhydrous THF (300 mL) and LiAlH4 (7.5 g, 200 mmol) was added in several small portions. After the addition was completed the mixture was stirred for 2 h at room temperature then cooled down to 0° C. and excess LiAlH4 was hydrolyzed by the addition of H2O (10 mL) and aq. HCl (2N, 200 mL). The resulting clear solution was extracted with EtOAc (3×200 mL) and the combined organic layers were dried (MgSO4) and evaporated under reduced pressure. The unpleasant smelling crude product (8.17 g, 104%) was carried on into the next step as obtained. 1H NMR (400 MHz, CDCl3): δ 7.17 (dd, 2H), 7.02 (t, 2H), 2.89 (t, 2H), 2.78 (dd, 2H), 1.38 (t, 1H). After the addition then cooled down to 0° C. The resulting clear solution was extracted with EtOAc (3×200 mL) the combined organic layers were dried (MgSO4) evaporated under reduced pressure as obtained

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Thioacetic acid S-[2-(4-fluoro-phenyl)-ethyl]ester (9.9 g, 50 mmol) was dissolved in anhydrous THF (300 mL) and LiAlH4 (7.5 g, 200 mmol) was added in several small portions. After the addition was completed the mixture was stirred for 2 h at room temperature then cooled down to 0° C. and excess LiAlH4 was hydrolyzed by the addition of H2O (10 mL) and aq. HCl (2N, 200 mL). The resulting clear solution was extracted with EtOAc (3×200 mL) and the combined organic layers were dried (MgSO4) and evaporated under reduced pressure. The unpleasant smelling crude product (8.17 g, 104%) was carried on into the next step as obtained. 1H NMR (400 MHz, CDCl3): δ 7.17 (dd, 2H), 7.02 (t, 2H), 2.89 (t, 2H), 2.78 (dd, 2H), 1.38 (t, 1H). After the addition then cooled down to 0° C. The resulting clear solution was extracted with EtOAc (3×200 mL) the combined organic layers were dried (MgSO4) evaporated under reduced pressure as obtained

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: The title compound was prepared from 3-(4-carboxymethyl-phenyl)-2-chloro-propionic acid 2,2,2-trichloro-ethyl ester (1.17 g, 3.13 mmol) and 2-(4-fluoro-phenyl)-ethanethiol (0.53 g, 3.44 mmol) as described for 3-[4-(tert-butyl-dimethyl-silanyloxy-methyl)-phenyl]-2-[2-(4-fluoro-phenyl)-ethylsulfanyl]-propionic acid methyl ester. After purification by flash chromatography with n-heptane/EtOAc 10:1 as the eluent the product was obtained as a solid (611 mg, 39.6%). 1H NMR (300 MHz, CDCl3): δ 7.09-7.23 (m, 6H), 6.94-6.99 (m, 2H), 4.65-4.77 (q, 2H), 3.56-3.61 (m, 3H), 3.18-3.28 (dd, 1H), 2.78-3.02 (m, 5H). After purification by flash chromatography with n-heptane/EtOAc 10:1 as the eluent the product

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: The title compound was prepared from 2-chloro-3-[4-(3-hydroxy-propyl)-phenyl]-propionic acid 2,2,2-trichloro-ethyl ester (0.74 g, 1.98 mmol) and 2-(4-fluoro-phenyl)-ethanethiol (0.34 g, 2.17 mmol) as described for 3-[4-(tert-butyl-dimethyl-silanyloxy-methyl)-phenyl]-2-[2-(4-fluoro-phenyl)-ethylsulfanyl]-propionic acid methyl ester. After repeated purification by flash chromatography with n-heptane/EtOAc 9:1 as the eluent the product was obtained as an oil (94 mg, 9.6%). 1H NMR (300 MHz, CDCl3): δ 7.10-7.11 (m, 6H), 6.94-6.98 (t, 2H), 4.65-4.75 (q, 2H), 3.64-3.68 (t, 2H), 3.58-3.61 (dd, 2H), 3.17-3.23 (dd, 2H), 2.80-2.97 (m, 5H), 2.65-2.70 (t, 2H), 1.86-1.89 (m, 2H). purification by flash chromatography with n-heptane/EtOAc 9:1 as the eluent the product

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: The title compound was prepared from 2-chloro-3-[4-(2-hydroxy-ethyl)-phenyl]-propionic acid 2,2,2-trichloro-ethyl ester (2.57 g, 7.14 mmol) and 2-(4-fluoro-phenyl)-ethanethiol (1.23 g, 7.85 mmol) as described for 3-[4-(tert-butyl-dimethyl-silanyloxy-methyl)-phenyl]-2-[2-(4-fluoro-phenyl)-ethylsulfanyl]-propionic acid methyl ester. After purification by flash chromatography with n-heptane/EtOAc 5:1 as the eluent the product was obtained as an oil (1.0 g, 29.2%). 1H NMR (300 MHz, CDCl3): δ 7.10-7.14 (m, 6H), 6.93-6.99 (t, 2H), 4.65-4.76 (q, 2H), 3.82-3.86 (t, 2H), 3.55-3.60 (dd, 2H), 3.17-3.25 (dd, 2H), 2.81-3.00 (m, 7H). After purification by flash chromatography with n-heptane/EtOAc 5:1 as the eluent the product

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 3-[4-(tert-butyl-dimethyl-silanyloxymethyl)-phenyl]-2-chloro-propionic acid methyl ester (6.56 g, 42 mmol) in anhydrous DMF (200 mL) was added Cs2CO3 (14.34 g, 44 mmol) at 0° C. After stirring for 30 min 2-(4-fluoro-phenyl)-ethanethiol (13.72 g, 40 mmol), dissolved in anhydrous DMF (100 mL), was added dropwise and the resulting organe mixture was stirred for 18 h without removing the cooling bath. The mixture was diluted with Et2O and extracted with three times with H2O. The organic phase was concentrated under reduced pressure and the residue was dissolved in Et2O again and repeatedly extracted with H2O. After drying the seperated organic layer over MgSO4, the solvent was removed under reduced pressure to afford the crude product as an orange oil which was purified by chromatography using n-heptane/EtOAc 20:1 as the eluent. The desired product was obtained as an oil (4.93 g, 25.4%). 1H NMR (400 MHz, CDCl3): δ 7.16 (d, 2H), 7.06-6.99 (m, 4H), 6.88 (t, 2H), 4.62 (s, 2H), 3.58 (s, 3H), 3.41 (dd, 1H), 3.10 (dd, 1H), 2.82 (dd, 1H), 2.74-2.76 (m, 4H), 0.85 (s, 9H), 0.00 (s, 6H). was added dropwise without removing the cooling bath The mixture was diluted with Et2O extracted with three times with H2O The organic phase was concentrated under reduced pressure the residue was dissolved in Et2O again repeatedly extracted with H2O After drying the seperated organic layer over MgSO4 the solvent was removed under reduced pressure to afford the crude product as an orange oil which was purified by chromatography