1-(1,3-BENZODIOXOL-5-YL)CYCLOPROPANECARBOXYLIC ACID

A mixture of 2-(benzo[d][1, 3]dioxol-5-yl)acetonitrile (5.10 g 31.7 mmol), 1-bromo-2-chloro-ethane (9.00 mL 109 mmol), and benzyltriethylammonium chloride (0.181 g, 0.795 mmol) was heated at 70° C. and then 50percent (wt./wt.) aqueous sodium hydroxide (26 mL) was slowly added to the mixture. The reaction was stirred at 70° C. for 24 hours and then heated at 130° C. for 48 hours. The dark brown reaction mixture was diluted with water (400 mL) and extracted once with an equal volume of ethyl acetate and once with an equal volume of dichloromethane. The basic aqueous solution was acidified with concentrated hydrochloric acid to pH less than one and the precipitate filtered and washed with 1 M hydrochloric acid. The solid material was dissolved in dichloromethane (400 mL) and extracted twice with equal volumes of 1 M hydrochloric acid and once with a saturated aqueous solution of sodium chloride. The organic solution was dried over sodium sulfate and evaporated to dryness to give a white to slightly off-white solid (5.23 g, 80percent) ESI-MS m/z calc. 206.1, found 207.1 (M+1)EXAMPLESPreparation of 1-benzo[1, 3]dioxol-5-yl-cyclopropanecarboxylic acid A mixture of 2-(benzo[d][1, 3]dioxol-5-yl)acetonitrile (5.10 g 31.7 mmol), 1-bromo-2-chloro-ethane (9.00 mL 109 mmol), and benzyltriethylammonium chloride (0.181 g, 0.795 mmol) was heated at 70° C. and then 50percent (wt./wt.) aqueous sodium hydroxide (26 mL) was slowly added to the mixture. The reaction was stirred at 70° C. for 24 hours and then heated at 130° C. for 48 hours. The dark brown reaction mixture was diluted with water (400 mL) and extracted once with an equal volume of ethyl acetate and once with an equal volume of dichloromethane. The basic aqueous solution was acidified with concentrated hydrochloric acid to pH less than one and the precipitate filtered and washed with 1 M hydrochloric acid. The solid material was dissolved in dichloromethane (400 mL) and extracted twice with equal volumes of 1 M hydrochloric acid and once with a saturated aqueous solution of sodium chloride. The organic solution was dried over sodium sulfate and evaporated to dryness to give a white to slightly off-white solid (5.23 g, 80percent) ESI-MS m/z calc. 206.1, found 207.1 (M+1)1. A mixture of 2-(benzo[d][1, 3]dioxol-5-yl)acetonitrile (5.10 g 31.7 mmol), 1-bromo-2-chloro-ethane (9.00 mL 109 mmol), and benzyltriethylammonium chloride (0.181 g, 0.795 mmol) was heated at 70° C. and then 50percent (wt./wt.) aqueous sodium hydroxide (26 mL) was slowly added to the mixture. A mixture of 2-(benzo[d][l, 3]dioxol-5-yl)acetonitrile (5.10 g 31.7 mmol), l-bromo-2- chloro-ethane (9.00 mL 109 mmol), and benzyltriethylammonium chloride (0.181 g, 0.795 mmol) was heated at 70 A mixture of benzo[1, 3]dioxole-5-acetonitrile (5.10 g 31.7 mmol), 1-bromo-2-chloro-ethane (9.00 mL 109 mmol), and benzyltriethylammonium chloride (0.181 g, 0.795 mmol) was heated at 70° C. and then 50percent (wt./wt.) aqueous sodium hydroxide (26 mL) was slowly added to the mixture. B. l-Benzori, 31dioxol-5-yl-cvclopropanecarboxylic acid; A mixture of benzo[l, 3]dioxole-5-acetonitrile (5.10 g, 31.7 mmol), l-bromo-2- chloro-ethane (9.0 mL, 109 mmol), and benzyltriethylammonium chloride (0.181 g, 0.795 mmol) was heated at 70 Example 19:; Hal = Cl, Br, I; General procedure:; Benzyltriethylammonium chloride (0.025 equivalents) and the appropriate dihalo compound (2.5 equivalents) was added to a substituted phenyl acetonitrile. The mixture was heated to 70 °C and then 50 percent sodium hydroxide (10 equivalents) was added dropwise. The reaction was stirred at 70 °C for 12-24 hours to insure complete formation of the cyclopropyl moity and then heated to 150 °C for 24-48 hours to insure complete conversion from the nitrile to the carboxylic acid. The dark brown/black reaction mixture was diluted with water and extracted with dichloromethane three times to remove side products. The basic aqueous solution was acidified with concentrated hydrochloric acid to pH less than one and the precipitate which began to form at pH 4 was filtered and washed with 1 M hydrochloric acid two times. The solid material was dissolved in dichloromethane and extracted two times with 1 M hydrochloric acid and one time with a saturated aqueous solution of sodium chloride. The organic solution was dried over sodium sulfate and evaporated to dryness to give the cyclopropanecarboxylic acid a white solid. Yields and purities were typically greater than 90 percent.; Specific Example:; l-Benzo [1, 3] dioxol-5-yl-cyclopropanecarboxylic acid.; A mixture of benzo [1, 3] dioxole-5- carbonitrile (5. 10g 31.7 mmol), 1-bromo-2-chloro-ethane (9. 000 mL 108.6 mmol), and benzyltriethylammonium chloride (0. 181 g 0.795 mmol) was heated to 70 °C and then 50 percent (wt. /wt. ) aqueous sodium hydroxide (26 mL) was slowly added. The reaction was stirred at 70 °C 'for 88 hours and then heated to 130 °C for 24 hours. The dark brown/black reaction mixture was diluted with water (400 mL) and extracted twice with equal volumes ethyl acetate and dichloromethane. The basic aqueous solution was acidified with concentrated hydrochloric acid to pH less than one and the precipitate was filtered and washed with 1 M hydrochloric acid. The solid material was dissolved in dichloromethane (400 mL) and extracted twice with equal volumes of 1 M hydrochloric acid and once with a saturated aqueous solution of sodium chloride. The organic solution was dried over sodium sulfate and evaporated to dryness to give a white to slightly off-white solid (5.23 g, 25.4, 80.1 percent. ESI-MS miz calc. 206.06, found 207.1 (M+1) +. Retention time of 2.37 minutes. 1H NMR (400 MHz, DMSO-d6) 8 1.07-1. 11 (m, 2H), 1. 38-1. 42 (m, 2H), 5.98 (s, 2H), 6.79 (m, 2H), 6. 88 (m, 1H), 12.26 (s, 1H)A mixture of benzo [1, 3] dioxole-5- carbonitrile (800 mg, 5 mmol), 1-bromo-2-chloro-ethane (1.4 ml, 17 mmol), and benzyltriethylammonium chloride (23 mg, 0.1 mmol) was heated to 75 °C and then 50percent (wt./wt.) aqueous sodium hydroxide (5 ml) was slowly added. The reaction was stirred at T = 75 °C for 24 h. After this time 1-bromo-2-chloro-ethane (700 μL, 8.5 mmol) and 50percent (wt./wt.) aqueous sodium hydroxide (1 mL) were added to insure complete formation of the cyclopropyl moiety (about 12 h). The reaction was then heated to T = 150 °C for about 48 h to insure complete conversion from the nitrile to the carboxylic acid. When the hydrolysis was complete (controlled with HPLC-MS) the dark brown mixture was diluted with water (10 ml) and extracted three times with equal volumes of dichloromethane to remove all the sub-products. The basic aqueous solution was acidified with concentrated hydrochloric acid to pH = 2. The reaction mixture was centrifuged at 4000g for 5 min and the pellet was washed with 1 M hydrochloric acid (3 * 1 ml). The solid material was dissolved in dichloromethane (5 ml) and extracted twice with equal volumes of 1 M hydrochloric acid. The organic phase was dried over Na

Molecular Weight:206.19
XLogP3:1.7
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:4
Rotatable Bond Count:2
Exact Mass:206.05790880
Monoisotopic Mass:206.05790880
Topological Polar Surface Area:55.8
Heavy Atom Count:15
Complexity:284
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes