methyl (1R,3S)-3-aminocyclopentane-1-carboxylate

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

実験手順: Using a method analogous to Method A, using (1R,3S)-methyl 3-aminocyclopentanecarboxylate and 2′,4′-difluorobiphenyl-4-sulphonyl chloride, the title compound was obtained as a pale yellow gum.

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

実験手順: Boc-anhydride (2.90 ml, 13.1 mmol) was added to a solution of (1R,3S)-methyl 3-aminocyclopentanecarboxylate (1.70 g, 11.9 mmol) and potassium carbonate (3.29 g, 23.8 mmol) in THF (10 ml), water (20 ml) and stirred for 24 h. The reaction mixture was extracted with DCM (2×50 ml). The combined organic layer was washed with water (20 ml), brine solution (20 ml), dried over anhydrous sodium sulfate, filtered and concentrated under vacuo to afford 2.5 g (87%) of tert-butyl (1S,3R)-3-(methoxycarbonyl)cyclopentylcarbamate as a colorless liquid. The reaction mixture was extracted with DCM (2×50 ml) The combined organic layer was washed with water (20 ml), brine solution (20 ml) dried over anhydrous sodium sulfate filtered concentrated under vacuo

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

実験手順: Potassium carbonate (462 mg, 3.30 mmol) was added to a solution of (1R,3S)-methyl 3-aminocyclopentanecarboxylate (400 mg, 2.22 mmol) in MeOH (10 ml) and stirred for 1 h. Benzyl bromide (0.2 ml, 1.8 mmol) was added to the reaction mixture and stirred for 15 h at 60-65° C. The reaction mixture was concentrated and the resulting residue was partitioned between water and CHCl3. The organic layer was separated and washed with water, brine solution, dried over anhydrous sodium sulfate, filtered and concentrated to afford the crude product. Purification by column chromatography over neutral alumina using 2% MeOH in CHCl3 as eluent afforded 180 mg of (1R,3S)-methyl 3-(benzylamino)cyclopentanecarboxylate with a purity of 75% which was proceeded for the next step. stirred for 15 h at 60-65° C The reaction mixture was concentrated the resulting residue was partitioned between water and CHCl3 The organic layer was separated washed with water, brine solution dried over anhydrous sodium sulfate filtered concentrated to afford the crude product Purification by column chromatography over neutral alumina using 2% MeOH in CHCl3 as eluent

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

実験手順: Acetic anhydride (0.07 ml, 7.00 mmol) was added to a stirred solution of (1R,3S)-methyl 3-aminocyclopentanecarboxylate (200 mg, 1.39 mmol) in pyridine (5 ml) and stirred for 15 h at ambient temperature. The reaction mixture was concentrated under reduced pressure, water and CHCl3 were added. The organic layer was separated and washed with saturated sodium bicarbonate solution, brine solution, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure to afford 180 mg (69%) of (1R,3S)-methyl 3-acetamidocyclopentanecarboxylate as brown oil. The reaction mixture was concentrated under reduced pressure, water and CHCl3 were added The organic layer was separated washed with saturated sodium bicarbonate solution, brine solution dried over anhydrous sodium sulfate filtered concentrated under reduced pressure

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

実験手順: Thionyl chloride (1.30 ml, 18.2 mmol) was added to a stirred solution of (1R,3S)-3-amino cyclo pentyl carboxylic acid (2.00 g, 12.1 mmol) in MeOH (20 ml) and refluxed for 3 h. The reaction mixture was concentrated under reduced pressure and co-distilled with toluene to afford 1.9 g (87%) of (1R,3S)-methyl 3-aminocyclopentanecarboxylate as off-white solid. refluxed for 3 h The reaction mixture was concentrated under reduced pressure and co-distilled with toluene

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

実験手順: Using a method analogous to Method A, using (1R,3S)-methyl 3-aminocyclopentanecarboxylate and 2′,4′-difluorobiphenyl-4-sulphonyl chloride, the title compound was obtained as a pale yellow gum.

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

実験手順: Using a method analogous to Method A, using (1R,3S)-methyl 3-aminocyclopentanecarboxylate and 2′,4′-difluorobiphenyl-4-sulphonyl chloride, the title compound was obtained as a pale yellow gum.

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

実験手順: Boc-anhydride (2.90 ml, 13.1 mmol) was added to a solution of (1R,3S)-methyl 3-aminocyclopentanecarboxylate (1.70 g, 11.9 mmol) and potassium carbonate (3.29 g, 23.8 mmol) in THF (10 ml), water (20 ml) and stirred for 24 h. The reaction mixture was extracted with DCM (2×50 ml). The combined organic layer was washed with water (20 ml), brine solution (20 ml), dried over anhydrous sodium sulfate, filtered and concentrated under vacuo to afford 2.5 g (87%) of tert-butyl (1S,3R)-3-(methoxycarbonyl)cyclopentylcarbamate as a colorless liquid. The reaction mixture was extracted with DCM (2×50 ml) The combined organic layer was washed with water (20 ml), brine solution (20 ml) dried over anhydrous sodium sulfate filtered concentrated under vacuo

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

実験手順: Potassium carbonate (462 mg, 3.30 mmol) was added to a solution of (1R,3S)-methyl 3-aminocyclopentanecarboxylate (400 mg, 2.22 mmol) in MeOH (10 ml) and stirred for 1 h. Benzyl bromide (0.2 ml, 1.8 mmol) was added to the reaction mixture and stirred for 15 h at 60-65° C. The reaction mixture was concentrated and the resulting residue was partitioned between water and CHCl3. The organic layer was separated and washed with water, brine solution, dried over anhydrous sodium sulfate, filtered and concentrated to afford the crude product. Purification by column chromatography over neutral alumina using 2% MeOH in CHCl3 as eluent afforded 180 mg of (1R,3S)-methyl 3-(benzylamino)cyclopentanecarboxylate with a purity of 75% which was proceeded for the next step. stirred for 15 h at 60-65° C The reaction mixture was concentrated the resulting residue was partitioned between water and CHCl3 The organic layer was separated washed with water, brine solution dried over anhydrous sodium sulfate filtered concentrated to afford the crude product Purification by column chromatography over neutral alumina using 2% MeOH in CHCl3 as eluent

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

実験手順: Acetic anhydride (0.07 ml, 7.00 mmol) was added to a stirred solution of (1R,3S)-methyl 3-aminocyclopentanecarboxylate (200 mg, 1.39 mmol) in pyridine (5 ml) and stirred for 15 h at ambient temperature. The reaction mixture was concentrated under reduced pressure, water and CHCl3 were added. The organic layer was separated and washed with saturated sodium bicarbonate solution, brine solution, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure to afford 180 mg (69%) of (1R,3S)-methyl 3-acetamidocyclopentanecarboxylate as brown oil. The reaction mixture was concentrated under reduced pressure, water and CHCl3 were added The organic layer was separated washed with saturated sodium bicarbonate solution, brine solution dried over anhydrous sodium sulfate filtered concentrated under reduced pressure

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

実験手順: Thionyl chloride (1.30 ml, 18.2 mmol) was added to a stirred solution of (1R,3S)-3-amino cyclo pentyl carboxylic acid (2.00 g, 12.1 mmol) in MeOH (20 ml) and refluxed for 3 h. The reaction mixture was concentrated under reduced pressure and co-distilled with toluene to afford 1.9 g (87%) of (1R,3S)-methyl 3-aminocyclopentanecarboxylate as off-white solid. refluxed for 3 h The reaction mixture was concentrated under reduced pressure and co-distilled with toluene

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

実験手順: Using a method analogous to Method A, using (1R,3S)-methyl 3-aminocyclopentanecarboxylate and 2′,4′-difluorobiphenyl-4-sulphonyl chloride, the title compound was obtained as a pale yellow gum.