3-ethoxycyclopent-2-en-1-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:

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

Procedure: A solution of 27.2 g (0.1 mole) of 1,4-dibromo-2,5-difluorobenzene in 200 ml of ether was blanketed with argon and cooled to -78° C. To this mixture was added 42 ml of n-butyl lithium (2.4 M; 0.10 mole) dropwise via an addition funnel. The solution was stirred at -78° C. for 15 minutes, then allowed to warm to -45° C. To the anion was added 13 ml of 3-ethoxy-2-cyclopentenone (0.10 mole); the solution was kept at -45° for 30 minutes and was then warmed slowly to room temperature. The mixture was poured into 250 ml of 1 N hydrochloric acid, stirred for 30 minutes, and extracted with ethyl acetate; the organic phases were combined, washed with water, dried over magnesium sulfate, and concentrated. The crude product was purified via silica gel chromatography using an 80:20 chloroform ethyl acetate mixture to give 14.2 g of the desired product; mp 129°-131° C. to warm to -45° C the solution was kept at -45° for 30 minutes was then warmed slowly to room temperature stirred for 30 minutes extracted with ethyl acetate washed with water dried over magnesium sulfate concentrated The crude product was purified via silica gel chromatography

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Isopropylmagnesium chloride (5 mL, 10 mmol, 2 M in diethyl ether) was placed in a dry flask and cooled to 0° C. 3-Ethoxycyclopentenone (0.88 g, 7 mmol) was added dropwise to the solution of the Grignard reagent, and the resulting mixture was stirred at room temperature for 23 h. At this point, 1 M HCl (15 mL) was added gradually, the aqueous phase was separated and extracted 3×with diethyl ether. The combined organic phases were dried over MgSO4, filtered, and concentrated in vacuo. The product was purified first by Kugelrohr distillation (0.1 torr, 120° C.), then by flash chromatography (1:1 pentane:ether) to afford the product as a colorless liquid (0.171 g, 20%). Spectroscopic data were consistent with previously reported data for this compound.7 the aqueous phase was separated extracted 3×with diethyl ether The combined organic phases were dried over MgSO4 filtered concentrated in vacuo The product was purified first by Kugelrohr distillation (0.1 torr, 120° C.)

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

Procedure: A solution of a Grignard reagent was prepared following the procedure described in the synthesis of 3-(5-hexenyl)cyclopent-2-enone, using Mg turnings (302 mg, 12 mmol), THF (11 mL), and benzyl 4-bromobutylether (2.75 g, 11.3 mmol). The general procedure for the preparation of substrates using 3-ethoxycyclopentenone (0.67 mL, 5.65 mmol), gave, after 12 h and flash chromatography (3:1, then 2:1 hexanes:ethyl acetate), the title compound as a white solid (0.662 g, 48%). m.p. 46-47° C. 1H NMR (300 MHz, CDCl3): δ 7.34-7.25 (m, 5H), 5.94 (s, 1H), 4.50 (s, 2H), 3.49 (t, J=6.0 Hz, 2H), 2.58-2.55 (m, 2H), 2.41-2.38 (m, 3H), 1.70-1.67 (m, 4H). 13C NMR (75 MHz, CDCl3): δ 210.2, 182.9, 138.6, 129.7, 128.6, 127.8 (2 peaks partially resolved), 73.3, 70.0, 35.6, 33.6, 31.8, 29.8, 24.2. IR (neat): 2941, 2853, 1710, 1613, 1451, 1366, 1185, 1119, 1000, 842, 749 cm−1. The general procedure for the preparation of substrates gave, after 12 h

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

Procedure: The general procedure for the preparation of substrates using 3-ethoxycyclopentenone (0.88 g, 7.0 mmol) and benzylmagnesium chloride (10 mmol, 1 M in diethyl ether) gave, after flash chromatography (2:1 hexanes:ethyl acetate) and Kugelrohr distillation (0.4 torr, 200° C.), the title compound as a white solid (0.58 g, 50%). m.p. 32-33° C. Spectroscopic data were consistent with previously reported data for this compound.3 The general procedure for the preparation of substrates gave after flash chromatography (2:1 hexanes:ethyl acetate) and Kugelrohr distillation (0.4 torr, 200° C.)

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

Procedure: A solution of a Grignard reagent was prepared following the procedure described in the synthesis of 3-(5-hexenyl)cyclopent-2-enone, using Mg turnings (302 mg, 12 mmol), THF (11 mL), and benzyl 4-bromobutylether (2.75 g, 11.3 mmol). The general procedure for the preparation of substrates using 3-ethoxycyclopentenone (0.67 mL, 5.65 mmol), gave, after 12 h and flash chromatography (3:1, then 2:1 hexanes:ethyl acetate), the title compound as a white solid (0.662 g, 48%). m.p. 46-47° C. 1H NMR (300 MHz, CDCl3): δ7.34-7.25 (m, 5 H), 5.94 (s, 1 H), 4.50 (s, 2 H), 3.49 (t, J=6.0 Hz, 2 H), 2.58-2.55 (m, 2 H), 2.41-2.38 (m, 3 H), 1.70-1.67 (m, 4 H). 13C NMR (75 MHz, CDCl3): δ210.2, 182.9, 138.6, 129.7, 128.6, 127.8 (2 peaks partially resolved), 73.3, 70.0, 35.6, 33.6, 31.8, 29.8, 24.2. IR (neat): 2941, 2853, 1710, 1613, 1451, 1366, 1185, 1119, 1000, 842, 749 cm−1. The general procedure for the preparation of substrates gave, after 12 h

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

Procedure: The general procedure for the preparation of substrates using 3-ethoxycyclopentenone (0.88 g, 7.0 mmol) and benzylmagnesium chloride (10 mmol, 1 M in diethyl ether) gave, after flash chromatography (2:1 hexanes:ethyl acetate) and Kugelrohr distillation (0.4 torr, 200° C.), the title compound as a white solid (0.58 g, 50%). m.p. 32-33° C. Spectroscopic data were consistent with previously reported data for this compound.3 The general procedure for the preparation of substrates gave after flash chromatography (2:1 hexanes:ethyl acetate) and Kugelrohr distillation (0.4 torr, 200° C.)

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

Procedure: The general procedure for the preparation of substrates using 3-ethoxycyclopentenone (0.88 g, 7.0 mmol) and benzylmagnesium chloride (10 mmol, 1 M in diethyl ether) gave, after flash chromatography (2:1 hexanes:ethyl acetate) and Kugelrohr distillation (0.4 torr, 200° C.), the title compound as a white solid (0.58 g, 50%). m.p. 32-33° C. Spectroscopic data were consistent with previously reported data for this compound.3 The general procedure for the preparation of substrates gave after flash chromatography (2:1 hexanes:ethyl acetate) and Kugelrohr distillation (0.4 torr, 200° C.)

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

Procedure: 3-Ethoxy-cyclopent-2-enone (Intermediate NINE1) (commercially available from Aldrich) (10.0 g, 77.6 mmol) in carbon tetrachloride (15 mL) at 0° C. was treated with NBS (15.3 g, ˜85 mmol) added portion-wise over 30 m. After 1 h at 0° C. the mixture was partitioned between CH2Cl2 and saturated NaHCO3. The aqueous layer was extracted with CH2Cl2. The pooled organic layers were washed with H2O (2×) and dried over MgSO4. The mixture was filtered and evaporated to dryness. The solid was recrystallized from pentane:ether to give 13.3 g of 2-bromo-3-ethoxy-cyclopent-2-enone (Intermediate NINE2). added portion-wise over 30 m After 1 h at 0° C. the mixture was partitioned between CH2Cl2 and saturated NaHCO3 The aqueous layer was extracted with CH2Cl2 The pooled organic layers were washed with H2O (2×) dried over MgSO4 The mixture was filtered evaporated to dryness The solid was recrystallized from pentane

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

Procedure: 3-Ethoxy-cyclopent-2-enone (Intermediate NINE1) (commercially available from Aldrich) (10.0 g, 77.6 mmol) in carbon tetrachloride (15 mL) at 0° C. was treated with NBS (15.3 g, ˜85 mmol) added portion-wise over 30 m. After 1 h at 0° C. the mixture was partitioned between CH2Cl2 and saturated NaHCO3. The aqueous layer was extracted with CH2Cl2. The pooled organic layers were washed with H2O (2×) and dried over MgSO4. The mixture was filtered and evaporated to dryness. The solid was recrystallized from pentane:ether to give 13.3 g of 2-bromo-3-ethoxy-cyclopent-2-enone (Intermediate NINE2). added portion-wise over 30 m After 1 h at 0° C. the mixture was partitioned between CH2Cl2 and saturated NaHCO3 The aqueous layer was extracted with CH2Cl2 The pooled organic layers were washed with H2O (2×) dried over MgSO4 The mixture was filtered evaporated to dryness The solid was recrystallized from pentane