2-acetylcyclopentan-1-one

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

Procedure: Using the same apparatus and procedure as described in Example 1, the onset temperature for a one gram sample of 82.5% di-2-ethylhexyl peroxydicarbonate diluted in OMS was measured. The procedure was repeated with separate samples of the above solution to which ethyl-2-cyclohexanone carboxylate, 2-acetyl cyclohexanone, 2-acetyl cyclopentanone, methyl-2-cycloheptanone carboxylate, ethyl-2-oxocyclopentane carboxylate, dibenzoyl methane, and ethyl-4-methyl-2-cyclohexanone-1-carboxylate had been added. The results are shown in Table II. Results obtained with ethyl acetoacetate, which is disclosed in the prior art, are included for comparison. had been added Results

Conditions: temp:23.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a round bottomed flask was loaded 3.78 grams of 2-acetylcyclopentanone, 3.52 grams of (5-Amino-1H-[1,2,4]triazol-3-yl)-methanol and 50 ml 2-methoxyethanol. The mixture was refluxed for 18 hours. Then it was cooled down to 23° C. and concentrated to 5 ml. Then 50 ml ethyl ether was added and the precipitate was filtered and vacuum dried to yielded 2.0 grams of product. This compound was used directly for the next step. MS: 205.2 (M+H). H-NMR (DMSO): δ 5.55 (t, 1H, OH, J=6.2 Hz), 4.63 (d, 2H, J=6.2 Hz), 3.28 (m, 2H), 3.02 (t, 2H, CH2, J=6.8 Hz), 2.51 (s, 3H, CH3), 2.27 (m, 2H, CH2). To a round bottomed flask was loaded The mixture was refluxed for 18 hours concentrated to 5 ml Then 50 ml ethyl ether was added the precipitate was filtered vacuum dried

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: First, 5.0 g (31 mmol) of L-glutamic acid-γ-methyl ester was suspended in 15 mL of methanol. To this, 4.3 g (34 mmol) of 2-acetyl-cyclopentanone and 3.1 g (31 mmol) of triethylamine were added. The mixture was heated at 60° C. for 2 hours. Subsequently, 20 g (310 mmol) of 70% ethylamine was added to the mixture and the same procedure as in Example 1 was performed to obtain 3.6 g of theanine (yield: 66.7%). The obtained theanine had the same purity as high as in Example 1.

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

Procedure: A procedure for the synthesis of pyrroles via N-(3-oxo-1-alkenyl)glycine ester was adapted from Hombrecher and Horter, Synthesis 389, 1990. Ethyl aminoacetate hydrochloride (28 g, 0.20 mol) and triethylamine (20.1 g, 0.20 mol) were added to a solution of 2-acetylcyclopentanone (25.0 g, 0.20mol) in ethanol (400 ml). The solution was stirred at room temperature for 15 hours and concentrated. The residue was combined with water (250 ml), and extracted with methylene chloride (4×100 ml). The combined extract was washed with water (100 ml), dried (sodium sulfate), and concentrated to leave a light brown oil. The oil was added with stirring at 50° C. to a solution of sodium ethoxide (14 g, 0.20 mol) in absolute ethanol (400 ml). The mixture was heated at 80° C. for 3 hours and poured into water (500 ml) to precipitate a light yellow solid. Recrystallization from ethanol gave ethyl 3-methyl-2,4,5,6-tetrahydrocyclopenta[c]pyrrolecarboxylate 4j, 9.1 g (24%)as a pale yellow solid, mp 166°-167° C.; 1H NMR (CDCl3): δ 8.38 (s, 1H), 4.24 (q, 2H), 2.78 (t, 2H), 2.52 (t, 2H), 2.30 (m, 2H), 2.18 (s, 3H), 1.30 (t, 3H). Anal. calcd for C11H15NO2 : C, 68.39; H, 7.77; N, 7.25. Found, C, 68.40; H, 7.85; N, 7.15. was adapted from Hombrecher and Horter, Synthesis 389, 1990 concentrated extracted with methylene chloride (4×100 ml) The combined extract was washed with water (100 ml) dried (sodium sulfate) concentrated to leave a light brown oil The oil was added The mixture was heated at 80° C. for 3 hours to precipitate a light yellow solid Recrystallization from ethanol

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

Procedure: A Knorr cyclization between ethyl a--aminoacetoacetate (prepared in situ) and a 3-alkyl-2,4-pentandione was selected for the preparation of ethyl alkylpyrrole-2 carboxylate derivatives 4b-f, i. Ethyl 3,5-dimethyl-4-tertbutylpyrrole-2-carboxylate 4g was prepared from ethyl 3,5-dimethylpyrrole-2-carboxylate 4a in an alkylation with tert-butyl acetate. In a modification of a Knoevenagel condensation of ethyl N-(3-oxo-1-alkenyl)aminoacetates to ethylpyrrole-2-carboxylates ethyl 3-methyl-2,4,-5,6-tetrahydrocyclopenta[c]pyrrolecarboxylate 4j was obtained by a base catalyzed cyclization of an unisolated enamine 13 (Table IV), in turn obtained from a condensation between glycine ethyl ester and α-acetylcyclopentanone. was obtained by a base

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

Procedure: To a solution of 2-acetyl-cyclopentanone (13.9 mg, 0.11 mol) and (R,R)-trans-1-[3,5-bis(trifluoromethyl)phenyl]-3-[2-(N,N-dimethylamino)cyclohexyl]thiourea (4.1 mg, 0.01 mmol) in toluene (1 mL) was added diisopropyl azodicarboxylate (21.5 μL, 0.10 mmol) at −78° C. After stirring for 18 hr, the reaction mixture was concentrated. The residue was purified by silica gel column (hexane/ethyl acetate=3/1) to give the title compound (31.8 mg, yield: 97%, optical purity: 77% ee). Colorless oil the reaction mixture was concentrated The residue was purified by silica gel column (hexane/ethyl acetate=3/1)

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

Procedure: 2-Acetyl cyclopentanone (0.12 mL, 1 mmol) and 2,6-dichloro-4-trifluoromethylphenylhydrazine (245 mg, 1 mmol) in EtOH (10 mL) was heated under reflux for 12 hr. EtOH was removed under reduced pressure and the product purified by flash chromatography on silica (10% EtOAc:Hexane): yield 75%. 1H NMR (CDCl3) δ 7.8 (s, 2H), 2.6 (m, 6H each), 2.2 (s, 3H); MS (M+) 335. under reflux for 12 hr EtOH was removed under reduced pressure the product purified by flash chromatography on silica (10% EtOAc:Hexane)

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

Procedure: Using the same apparatus and procedure as described in Example 1, the onset temperature for a one gram sample of 82.5% di-2-ethylhexyl peroxydicarbonate diluted in OMS was measured. The procedure was repeated with separate samples of the above solution to which ethyl-2-cyclohexanone carboxylate, 2-acetyl cyclohexanone, 2-acetyl cyclopentanone, methyl-2-cycloheptanone carboxylate, ethyl-2-oxocyclopentane carboxylate, dibenzoyl methane, and ethyl-4-methyl-2-cyclohexanone-1-carboxylate had been added. The results are shown in Table II. Results obtained with ethyl acetoacetate, which is disclosed in the prior art, are included for comparison. had been added Results

Conditions: temp:23.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a round bottomed flask was loaded 3.78 grams of 2-acetylcyclopentanone, 3.52 grams of (5-Amino-1H-[1,2,4]triazol-3-yl)-methanol and 50 ml 2-methoxyethanol. The mixture was refluxed for 18 hours. Then it was cooled down to 23° C. and concentrated to 5 ml. Then 50 ml ethyl ether was added and the precipitate was filtered and vacuum dried to yielded 2.0 grams of product. This compound was used directly for the next step. MS: 205.2 (M+H). H-NMR (DMSO): δ 5.55 (t, 1H, OH, J=6.2 Hz), 4.63 (d, 2H, J=6.2 Hz), 3.28 (m, 2H), 3.02 (t, 2H, CH2, J=6.8 Hz), 2.51 (s, 3H, CH3), 2.27 (m, 2H, CH2). To a round bottomed flask was loaded The mixture was refluxed for 18 hours concentrated to 5 ml Then 50 ml ethyl ether was added the precipitate was filtered vacuum dried