methyl 2-(3-oxocyclopentyl)acetate

反応条件: temp:0.00; pressure:0.00; stir:

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

実験手順: Tetrahedron, 57 (2001), 5183. A mixture of Montmorillonite K10 (188 g, 571 mmol) in trimethyl orthoformate (316 mL, 2856 mmol) was stirred for 2 hrs under nitrogen. To the mixture was slowly added methyl 2-(3-oxocyclopentyl)acetate (89.2 g, 571 mmol), as a suspension in pentane (500 mL). The mixture was stirred for 16 hrs, then filtered through a CELITE® pad rinsing with pentane. The filtrate was concentrated under reduced pressure to afford the title compound (104.9 g, 519 mmol, 91% yield) as an amber oil. 1H NMR (400 MHz, CDCl3) δ ppm 3.67 (3 H, s) 3.20 (6 H, s) 2.35-2.46 (3 H, m) 2.11 (1 H, dd, J=13.18, 7.40 Hz) 1.86-1.96 (2 H, m) 1.74-1.83 (1 H, m) 1.44 (1 H, dd, J=13.05, 8.53 Hz) 1.34 (1 H, dd, J=12.55, 8.78 Hz). 13C NMR (101 MHz, CDCl3) δ ppm 172.73, 110.91, 50.93, 48.80, 48.61, 40.27, 39.66, 33.51, 33.25, 29.37. The mixture was stirred for 16 hrs filtered through a CELITE® pad rinsing with pentane The filtrate was concentrated under reduced pressure

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

実験手順: Tetrahedron, 57 (2001), 5183. A mixture of Montmorillonite K10 (188 g, 571 mmol) in trimethyl orthoformate (316 mL, 2856 mmol) was stirred for 2 hrs under nitrogen. To the mixture was slowly added methyl 2-(3-oxocyclopentyl)acetate (89.2 g, 571 mmol), as a suspension in pentane (500 mL). The mixture was stirred for 16 hrs, then filtered through a CELITE® pad rinsing with pentane. The filtrate was concentrated under reduced pressure to afford the title compound (104.9 g, 519 mmol, 91% yield) as an amber oil. 1H NMR (400 MHz, CDCl3) δ ppm 3.67 (3 H, s) 3.20 (6 H, s) 2.35-2.46 (3 H, m) 2.11 (1 H, dd, J=13.18, 7.40 Hz) 1.86-1.96 (2 H, m) 1.74-1.83 (1 H, m) 1.44 (1 H, dd, J=13.05, 8.53 Hz) 1.34 (1 H, dd, J=12.55, 8.78 Hz). 13C NMR (101 MHz, CDCl3) δ ppm 172.73, 110.91, 50.93, 48.80, 48.61, 40.27, 39.66, 33.51, 33.25, 29.37. The mixture was stirred for 16 hrs filtered through a CELITE® pad rinsing with pentane The filtrate was concentrated under reduced pressure

反応条件: temp:210.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A 1000 mL flask was charged with dimethyl 2-(3-oxocyclopentyl)malonate (329.1 g, 1536 mmol), and dodecanedioic acid (283 g, 1229 mmol). The mixture was heated (210° C., oil bath) under a nitrogen atmosphere for 20 hrs, then distilled (˜1 torr, 180° C. oil bath) to give the title compound (170.4 g, 1091 mmol, 71.0% yield) as a pale yellow oil. 1H NMR (500 MHz, CDCl3) δ ppm 3.68 (3 H, s), 2.55-2.66 (1 H, m), 2.40-2.51 (3 H, m), 2.27-2.35 (1 H, m), 2.13-2.26 (2 H, m), 1.87 (1 H, ddd, J=18.23, 10.30, 1.37 Hz), 1.53-1.63 (1 H, m). 13C NMR (126 MHz, CDCl3) δ ppm 218.36, 172.58, 51.78, 44.70, 39.53, 38.40, 33.52, 29.31. distilled (˜1 torr, 180° C. oil bath)

反応条件: temp:0.00; pressure:0.00; stir:

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

実験手順: The reductive amination of (S)-2-amino-6-(5-amino-2-fluoro-phenyl)-3,5,5,6-tetramethyl-5,6-dihydro-3H-pyrimidin-4-one (intermediate J) and (3-oxo-cyclopentyl)-acetic acid methyl ester using decaborane yielded a mixture of isomers of the title compound as a white foam. MS (ESI): m/z=419.3 [M+H]+. yielded

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

実験手順: The reductive amination of (S)-2-amino-6-(5-amino-2-fluoro-phenyl)-3,5,5,6-tetramethyl-5,6-dihydro-3H-pyrimidin-4-one (intermediate J) and (3-oxo-cyclopentyl)-acetic acid methyl ester using decaborane yielded a mixture of isomers of the title compound as a white foam. MS (ESI): m/z=419.3 [M+H]+. yielded

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 following the procedure described in method 2 for the preparation of intermediate 1, Step 6, using methyl 2-(3-oxocyclopentyl)acetate as the reactant. (50.1% yield). 1H NMR (400 MHz, CHLOROFORM-d) δ 5.66 (q, J=2.1 Hz, 1H), 3.73 (br. s., 3H), 3.29-3.13 (m, 1H), 2.95-2.78 (m, 1H), 2.67-2.57 (m, 2H), 2.49-2.40 (m, 1H), 2.40-2.28 (m, 1H), 1.77-1.63 (m, 1H). 19F NMR (376 MHz, CHLOROFORM-d) δ −73.53 (s, 3F).

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

実験手順: Tetrahedron, 57 (2001), 5183. A mixture of Montmorillonite K10 (188 g, 571 mmol) in trimethyl orthoformate (316 mL, 2856 mmol) was stirred for 2 hrs under nitrogen. To the mixture was slowly added methyl 2-(3-oxocyclopentyl)acetate (89.2 g, 571 mmol), as a suspension in pentane (500 mL). The mixture was stirred for 16 hrs, then filtered through a CELITE® pad rinsing with pentane. The filtrate was concentrated under reduced pressure to afford the title compound (104.9 g, 519 mmol, 91% yield) as an amber oil. 1H NMR (400 MHz, CDCl3) δ ppm 3.67 (3 H, s) 3.20 (6 H, s) 2.35-2.46 (3 H, m) 2.11 (1 H, dd, J=13.18, 7.40 Hz) 1.86-1.96 (2 H, m) 1.74-1.83 (1 H, m) 1.44 (1 H, dd, J=13.05, 8.53 Hz) 1.34 (1 H, dd, J=12.55, 8.78 Hz). 13C NMR (101 MHz, CDCl3) δ ppm 172.73, 110.91, 50.93, 48.80, 48.61, 40.27, 39.66, 33.51, 33.25, 29.37. The mixture was stirred for 16 hrs filtered through a CELITE® pad rinsing with pentane The filtrate was concentrated under reduced pressure

反応条件: temp:210.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A 1000 mL flask was charged with dimethyl 2-(3-oxocyclopentyl)malonate (329.1 g, 1536 mmol), and dodecanedioic acid (283 g, 1229 mmol). The mixture was heated (210° C., oil bath) under a nitrogen atmosphere for 20 hrs, then distilled (˜1 torr, 180° C. oil bath) to give the title compound (170.4 g, 1091 mmol, 71.0% yield) as a pale yellow oil. 1H NMR (500 MHz, CDCl3) δ ppm 3.68 (3 H, s), 2.55-2.66 (1 H, m), 2.40-2.51 (3 H, m), 2.27-2.35 (1 H, m), 2.13-2.26 (2 H, m), 1.87 (1 H, ddd, J=18.23, 10.30, 1.37 Hz), 1.53-1.63 (1 H, m). 13C NMR (126 MHz, CDCl3) δ ppm 218.36, 172.58, 51.78, 44.70, 39.53, 38.40, 33.52, 29.31. distilled (˜1 torr, 180° C. oil bath)

反応条件: temp:0.00; pressure:0.00; stir: