* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
With ruthenium trichloride; sodium periodate In water; ethyl acetate; acetonitrile at 5 - 39℃; Industry scale
A 22-L, 3-neck, round bottom flask was equipped with a mechanical stirrer, a J-KEM temperature controller, and anitrogen inlet. The flask was charged with norbornene (200 g, 2.123 mol), ethyl acetate(1.95 L), and acetonitrile (1.95 L). The reaction mixture was cooled to 5 °C using anacetone/dry ice bath. Ruthenium trichloride (9.69 g, 46.72 mmol) was added in oneportion followed by the slow addition of a suspension of sodium periodate (1.816 kg,8.707 mol) in water (2.925 L) over 30 min. The reaction slowly began to exotherm and was monitored to keep the temperature between 10 °C and 15 °C. After 90 min thereaction mixture suddenly thickened to the point where stirring was difficult andexothermed rapidly up to 39 °C (a large amount of dry ice was added to the cooling bath to control the exotherm). The reaction mixture was allowed to cool to 20 °C, the dryice/acetone bath was removed, and the mixture was stirred at room temperature overnight.The solids were removed by filtration through a pad of celite and the filtrate wasconcentrated to a solid which was triturated with hexane (2 L), filtered, and rinsed with hexane (2 x 500 mL) to yield 195 g (58percent) of cyclopentane-l,3-dicarboxylic acid.1H NMR (500 Hz, DMSO-<3/4) δ ppm 12.07 (s, 2H), 2.66-2.73 (m, 2H), 2.06-2.12 (m, 1H), 1.85-1.89 (m, 1H), 1.72-1.85 (m, 4H).
53%
With sodium periodate; water In chloroform at 20℃; for 48 h;
A mixture of commercially available norbonene (15 g) and RuCl3 (0.3 g) in CHCl3 (100 mL) was stirred at room temperature for 5 min. Then a solution OfNaIO4 (163 g) in H2O (1200 mL) was added and the mixture was stirred at room temperature for 2 d. The mixture was filtered through a pad of celite.(R). and the organic phase was separated. The aqueous phase was saturated with NaCl and extracted with EtOAc (3 x 500 mL). The combined organic phases were treated with MgSO4 and charcoal, filtered and concentrated to afford the crude title compound as thick slightly purple liquid (13.5 g, 53percent). [MH]+ = 159.
Reference：
[1] Tetrahedron Letters, 2005, vol. 46, # 18, p. 3201 - 3203
[2] Russian Journal of Applied Chemistry, 2011, vol. 84, # 2, p. 236 - 242
[3] Tetrahedron Letters, 2010, vol. 51, # 23, p. 3123 - 3126
[4] Australian Journal of Chemistry, 1985, vol. 38, # 11, p. 1705 - 1718
[5] Journal of Medicinal Chemistry, 2011, vol. 54, # 10, p. 3480 - 3491
[6] Patent: WO2012/145569, 2012, A1, . Location in patent: Page/Page column 179
[7] Patent: WO2006/128184, 2006, A2, . Location in patent: Page/Page column 167
[8] Journal of Organic Chemistry, 1993, vol. 58, # 17, p. 4745
[9] Journal of Organic Chemistry, 1963, vol. 28, p. 2537 - 2541
2
[ 497-38-1 ]
[ 4056-78-4 ]
Reference：
[1] Chemical and Pharmaceutical Bulletin, 1961, vol. 9, p. 391 - 403
3
[ 18084-03-2 ]
[ 4056-78-4 ]
Reference：
[1] Chemical and Pharmaceutical Bulletin, 1961, vol. 9, p. 391 - 403
4
[ 71720-43-9 ]
[ 4056-78-4 ]
Reference：
[1] Chemical and Pharmaceutical Bulletin, 1961, vol. 9, p. 391 - 403
A 5-L, 3-neck, roundbottom flask was equipped with a mechanical stirrer, a J-KEM temperature controller, and a reflux condenser. The flask was charged with cyclopentane-l,3-dicarboxylic acid(357 g, 2.262 mol) and methanol (1.75 L). The solution was cooled to 7 °C using anice/water bath. Concentrated sulfuric acid (70 mL) was added dropwise over 30 minresulting in an exotherm up to 12 °C. The reaction mixture was heated to reflux andstirred for 16 h when TLC analysis (10 percent methanol/ethyl acetate) indicated that thereaction was complete. The reaction mixture was concentrated, redissolved in methyl- 179 -ATI-2514175vl tert-butyl ether, and washed with saturated aqueous sodium bicarbonate (2 x 150 mL) and brine (2 x 150 mL). The organic layer was dried over sodium sulfate, filtered, and concentrated. The resulting clear oil was dissolved in hexane (2 L) and treated with a 2 N aqueous sodium hydroxide solution (950 mL) until the pH ~ 10. The layers were separated and the aqueous layer was extracted with hexane (4 x 1 L). The organic layers were combined, dried over sodium sulfate, filtered, and concentrated to provide 360 g (100percent) of dimethyl cyclopentane-l,3-dicarboxylate as a clear oil. 1H NMR (500 Hz, CDCls) δ ppm 3.67 (s, 6H), 2.75-2.83 (m, 2H), 2.20-2.26 (m, 1H), 2.05-2.12 (m, 1H), 1.90-2.0 (m, 4H).
88%
With sulfuric acid In water at 0 - 90℃;
Step A: Dimethyl cyclopentane-1,3-dicarboxylate. A solution of cyclopentane-1,3-dicarboxylic acid (70.0 g, 443 mmol) and anhydrous methanol (300 mL) was cooled to 0° C. in an ice water bath. Concentrated sulfuric acid (14 mL) was added dropwise, maintaining the temperature at <15° C. After the addition, the reaction was heated to 90° C. and stirred overnight. The reaction was cooled to room temperature and concentrated to dryness. The residue was treated with MTBE (500 mL) and H2O (100 mL). The aqueous layer was separated and extracted with MTBE (2*100 mL). The combined organic extracts were washed with saturated sodium bicarbonate (2*100 mL), brine (100 mL), dried over anhydrous MgSO4, filtered, and concentrated to dryness to provide the title compound (72.5 g, 88percent) as a pale yellow oil. 1H NMR (400 MHz, CDCl3) δ 3.65 (s, 6H), 2.84-2.72 (m, 2H), 2.26-2.17 (m, 1H), 2.11-2.02 (m, 1H), 1.96-1.88 (m, 4H).
88%
at 15 - 90℃;
. A solution of cyclopentane-1,3- dicarboxylic acid (70.0 g, 443 mmol) and anhydrous methanol (300 mL) was cooled to 0 °C in an ice water bath. Concentrated sulfuric acid (14 mL) was added dropwise, maintaining the temperature at < 15 °C. After the addition, the reaction was heated to 90 °C and stirred overnight. The reaction was cooled to room temperature and concentrated to dryness. Theresidue was treated with MTBE (500 mL) and H20 (100 mL). The aqueous layer was separated and extracted with MTBE (2 x 100 mL). The combined organic extracts were washed with saturated sodium bicarbonate (2 x 100 mL), brine (100 mL), dried over anhydrous Mg504, filtered, and concentrated to dryness to provide the title compound (72.5 g, 88percent) as a pale yellow oil. ‘HNMR(400 IVIFIz, CDC13) 3.65 (s, 6H), 2.84-2.72 (m, 2H), 2.26-2.17 (m, 1H),2.11 -2.02(m, 1H), 1.96- 1.88(m,4H).
64%
at 20℃; for 15 h; Heating / reflux
To a solution of the title compound from Step A above (11.2 g) in MeOH (250 mL) was added concentrated H2SO4 (0.5 mL) at room temperature. The mixture was heated to reflux for 15 h, cooled to room temperature, filtrated and concentrated. The remaining residue was diluted with EtOAc (100 mL), washed with saturated aqueous NaHCO3 (3 x 50 mL) and saturated aqueous NaCl (50 mL), dried (MgSO4), filtered, concentrated and purified by chromatography (silica, cyclohexane/EtOAc) to afford the title compound as a colorless solid (8.43 g, 64percent). [MH]+ = 187.
Reference：
[1] Patent: WO2012/145569, 2012, A1, . Location in patent: Page/Page column 179; 180
[2] Journal of Medicinal Chemistry, 2011, vol. 54, # 10, p. 3480 - 3491
[3] Patent: US2018/170931, 2018, A1, . Location in patent: Paragraph 0188
[4] Patent: WO2018/112382, 2018, A1, . Location in patent: Page/Page column 174
[5] Tetrahedron Letters, 2005, vol. 46, # 18, p. 3201 - 3203
[6] Patent: WO2006/128184, 2006, A2, . Location in patent: Page/Page column 167
[7] Australian Journal of Chemistry, 1985, vol. 38, # 11, p. 1705 - 1718
[8] Patent: WO2016/106623, 2016, A1, . Location in patent: Page/Page column 113
[9] Patent: WO2016/106624, 2016, A1, . Location in patent: Page/Page column 64
A 5-L, 3-neck, roundbottom flask was equipped with a mechanical stirrer, a J-KEM temperature controller, and a reflux condenser. The flask was charged with cyclopentane-l,3-dicarboxylic acid(357 g, 2.262 mol) and methanol (1.75 L). The solution was cooled to 7 C using anice/water bath. Concentrated sulfuric acid (70 mL) was added dropwise over 30 minresulting in an exotherm up to 12 C. The reaction mixture was heated to reflux andstirred for 16 h when TLC analysis (10 % methanol/ethyl acetate) indicated that thereaction was complete. The reaction mixture was concentrated, redissolved in methyl- 179 -ATI-2514175vl tert-butyl ether, and washed with saturated aqueous sodium bicarbonate (2 x 150 mL) and brine (2 x 150 mL). The organic layer was dried over sodium sulfate, filtered, and concentrated. The resulting clear oil was dissolved in hexane (2 L) and treated with a 2 N aqueous sodium hydroxide solution (950 mL) until the pH ~ 10. The layers were separated and the aqueous layer was extracted with hexane (4 x 1 L). The organic layers were combined, dried over sodium sulfate, filtered, and concentrated to provide 360 g (100%) of dimethyl cyclopentane-l,3-dicarboxylate as a clear oil. 1H NMR (500 Hz, CDCls) delta ppm 3.67 (s, 6H), 2.75-2.83 (m, 2H), 2.20-2.26 (m, 1H), 2.05-2.12 (m, 1H), 1.90-2.0 (m, 4H).
88%
With sulfuric acid; In water; at 0 - 90℃;
Step A: Dimethyl cyclopentane-1,3-dicarboxylate. A solution of <strong>[4056-78-4]cyclopentane-1,3-dicarboxylic acid</strong> (70.0 g, 443 mmol) and anhydrous methanol (300 mL) was cooled to 0 C. in an ice water bath. Concentrated sulfuric acid (14 mL) was added dropwise, maintaining the temperature at <15 C. After the addition, the reaction was heated to 90 C. and stirred overnight. The reaction was cooled to room temperature and concentrated to dryness. The residue was treated with MTBE (500 mL) and H2O (100 mL). The aqueous layer was separated and extracted with MTBE (2*100 mL). The combined organic extracts were washed with saturated sodium bicarbonate (2*100 mL), brine (100 mL), dried over anhydrous MgSO4, filtered, and concentrated to dryness to provide the title compound (72.5 g, 88%) as a pale yellow oil. 1H NMR (400 MHz, CDCl3) delta 3.65 (s, 6H), 2.84-2.72 (m, 2H), 2.26-2.17 (m, 1H), 2.11-2.02 (m, 1H), 1.96-1.88 (m, 4H).
88%
With sulfuric acid; at 15 - 90℃;
. A solution of cyclopentane-1,3- dicarboxylic acid (70.0 g, 443 mmol) and anhydrous methanol (300 mL) was cooled to 0 C in an ice water bath. Concentrated sulfuric acid (14 mL) was added dropwise, maintaining the temperature at < 15 C. After the addition, the reaction was heated to 90 C and stirred overnight. The reaction was cooled to room temperature and concentrated to dryness. Theresidue was treated with MTBE (500 mL) and H20 (100 mL). The aqueous layer was separated and extracted with MTBE (2 x 100 mL). The combined organic extracts were washed with saturated sodium bicarbonate (2 x 100 mL), brine (100 mL), dried over anhydrous Mg504, filtered, and concentrated to dryness to provide the title compound (72.5 g, 88%) as a pale yellow oil. ?HNMR(400 IVIFIz, CDC13) 3.65 (s, 6H), 2.84-2.72 (m, 2H), 2.26-2.17 (m, 1H),2.11 -2.02(m, 1H), 1.96- 1.88(m,4H).
88%
With sulfuric acid; at 15 - 90℃;
A solution of cyclopentane-l,3- dicarboxylic acid (70.0 g, 443 mmol) and anhydrous methanol (300 mL) was cooled to 0 C in an ice water bath. Concentrated sulfuric acid (14 mL) was added drop wise, maintaining the temperature at < 15 C. After the addition, the reaction was heated to 90 C and stirred overnight. The reaction was cooled to room temperature and concentrated to dryness. The residue was treated with MTBE (500 mL) and H2O (100 mL). The aqueous layer was separated and extracted with MTBE (2 x 100 mL). The combined organic extracts were washed with saturated sodium bicarbonate (2 x 100 mL), brine (100 mL), dried over anhydrous MgS04, filtered, and concentrated to dryness to provide the title compound (72.5 g, 88%) as a pale yellow oil. NMR (400 MHz, CDCb) d 3.65 (s, 6H), 2.84 - 2.72 (m, 2H), 2.26 - 2.17 (m, 1H), 2.11 - 2.02 (m, 1H), 1.96 - 1.88 (m, 4H).
64%
With sulfuric acid; at 20℃; for 15.0h;Heating / reflux;
To a solution of the title compound from Step A above (11.2 g) in MeOH (250 mL) was added concentrated H2SO4 (0.5 mL) at room temperature. The mixture was heated to reflux for 15 h, cooled to room temperature, filtrated and concentrated. The remaining residue was diluted with EtOAc (100 mL), washed with saturated aqueous NaHCO3 (3 x 50 mL) and saturated aqueous NaCl (50 mL), dried (MgSO4), filtered, concentrated and purified by chromatography (silica, cyclohexane/EtOAc) to afford the title compound as a colorless solid (8.43 g, 64%). [MH]+ = 187.
With oxalyl dichloride; at 20℃;Inert atmosphere; Cooling with ice;
Oxalyl dichloride (10.03 g, 79 mmol) was added to a solution of cyclopentane-1, 3-dicarboxylic acid (5g, 31.6 mmol) in dry MeOH (50 mL) under argon in an ice-water bath. The solution was allowed to warm to room temperature and stirred overnight. Volatiles were then removed under vacuum. The residue was taken up in EtOAc (2×50 mL) and the solution was washed with NaHCO3(2×50 mL) and brine (50 mL) , dried over MgSO4, filtered, and concentrated to give the title compound.1H NMR (400 MHz, CDCl3) : 3.70 (s, 6H) , 2.75-2.90 (m, 2H) , 2.20-2.30 (m, 1H) , 2.10-2.20 (m, 1H) , 1.90-2.20 (m, 4H) ppm.
With oxalyl dichloride; at 20℃;Inert atmosphere; Cooling with ice;
Oxalyl dichloride (10.03 g, 79 mmol) was added to a solution of cyclopentane-1, 3-dicarboxylic acid (5g, 31.6 mmol) in dry MeOH (50 mL) under argon in an ice-water bath. The solution was allowed to warm to room temperature and stirred overnight. Volatiles were then removed under vacuum. The residue was taken up in EtOAc (2 × 50 mL) and the solution was washed with NaHCO3 (2 × 50 mL) and brine (50 mL) , dried over MgSO4, filtered, and concentrated to give the title compound. 1H NMR (400 MHz, CDCl3) : delta3.70 (s, 6H) , 2.75-2.90 (m, 2H) , 2.20-2.30 (m, 1H), 2.10-2.20 (m, 1H) , 1.90-2.20 (m, 4H) .
4-(4-(quinolin-2-yl)piperazin-1-yl)butan-1-amine[ No CAS ]
[ 4056-78-4 ]
3-[4-[4-(2-quinolyl)-1-piperazinyl]butyl]-3-azabicyclo[3.2.1]octane-2,4-dione[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
In 5,5-dimethyl-1,3-cyclohexadiene; ethanol; chloroform;
EXAMPLE 9 3-[4-[4-(2-Quinolyl)-1-piperazinyl]butyl]-3-azabicyclo[3.2.1]octane-2,4-dione 1,3-Cyclopentane dicarboxylic acid (1.6 g., 10 mmole) and 1-(4-aminobutyl)-4-(2-quinolyl)piperazine (2.8 g., 10 mmole) were combined in 200 ml. of xylene and refluxed for 24 hours with water removal via a Dean-Stark trap. The solvent was then removed in vacuum and the residue redissolved in chloroform and filtered through 75 g. of silica gel. The column was rinsed with 5% ethanol/chloroform and the product-containing fractions were combined and evaporated. The residue was recrystallized from isopropanol with the addition of 4N isopropanolic HCl to give 820 mg. of the title compound as the dihydrochloride hemihydrate; m.p. 240-242 C. Elemental Analysis: C24 H30 N4 O2.2HCl.1/2H2 O. Calculated: C, 59.02; H, 6.81; N, 11.47. Found: C, 58.93; H, 6.59; N, 11.35.
3-[4-[4-(2-pyrimidinyl)-1-piperazinyl]butyl]-3-azabicyclo[3.2.1]octane-2,4-dione[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
With hydrogenchloride; In ethanol; dichloromethane; acetic anhydride; isopropyl alcohol; toluene;
EXAMPLE 2 3-[4-[4-(2-Pyrimidinyl)-1-piperazinyl]butyl]-3-azabicyclo[3.2.1]octane-2,4-dione <strong>[4056-78-4]1,3-Cyclopentanedicarboxylic acid</strong> (4.0 g., 25 mmole) was converted to the anhydride by refluxing for 3 hours in 20 ml. of acetic anhydride. After removal of excess acetic anhydride, extraction with hexane and evaporation of the hexane, 3.95 g. of cyclopentane-1,3-dicarboxylic anhydride was obtained. The anhydride was combined with 6.51 g. (27 mmole) of 1-(4-aminobutyl)-4-(2-pyrimidinyl)piperazine in 50 ml. of dichloromethane and stirred at room temperature overnight. The dichloromethane was removed in vacuo and replaced with 75 ml. of toluene. The mixture was refluxed for 24 hours with water separation via a Dean-Stark trap. The product was concentrated under vacuum and chromatographed on 200 g. of silica gel with 5% ethanol/chloroform. The product-containing fractions were combined and concentrated and the residue crystallized (2 crops) from isopropanol with addition of 4N HCl/isopropanol. A second recrystallization from isopropanol gave 1.1 g. of the title compound as the dihydrochloride, hemihydrate; m.p. 201-203 C.(d). Elemental Analysis: C19 H27 N5 O2.2HCl.1/22H2 O. Calculated: C, 51.94; H, 6.88; N, 15.94. Found: C, 51.97; H, 6.66; N, 15.93.
3-[4-[4-(2-Methoxyphenyl)-1-piperazinyl]butyl]-3-azabicyclo[3.2.1]octane-2,4-dione[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
With acetic anhydride; In 5,5-dimethyl-1,3-cyclohexadiene; ethanol; chloroform; isopropyl alcohol;
EXAMPLE 17 3-[4-[4-(2-Methoxyphenyl)-1-piperazinyl]butyl]-3-azabicyclo[3.2.1]octane-2,4-dione 1,3-Cyclopentane dicarboxylic acid (2.4 g., 15 mmole) was treated at reflux with 100 ml. of acetic anhydride for 3 hours. The anhydride thus formed was concentrated and stored in vacuum. It was combined with 4.0 g. (15 mmole) of 1-(4-aminobutyl)-4-(2-methoxyphenyl)piperazine in 300 ml. of xylene and refluxed for 48 hours with water removal via a Dean-Stark trap. The reaction was allowed to cool and filtered through 75 g. of silica gel using 2% ethanol in chloroform as eluent. Concentration in vacuum and recrystallization from 75 ml. of isopropanol with addition of 4N isopropanolic HCl gave 3.5 g. of the title compound as the dihydrochloride; m.p. 215.5-216.5 C. Elemental Analysis: C22 H31 N3 O3.2HCl. Calculated: C, 57.64; H, 7.26; N, 9.17. Found: C, 57.41; H, 7.41; N, 9.13.
With caesium carbonate; In N,N-dimethyl-formamide; at 20℃; for 3.0h;Inert atmosphere;
To a mixture of cis and trans-<strong>[4056-78-4]cyclopentyl 1,3-dicarboxylic acid</strong> (1.58 g, 10.0 mmol), Cs2CO3 (8.28 g, 25.5 mmol) in DMF (20 mL) was added BnBr (4.36 g, 25.5 mmol). The mixture was stirred at rt under nitrogen for 3 h. The residue was diluted with water and extracted with ethyl acetate. The combined organic solution was washed with water, dried over Na2SO4 and concentrated in vacuo. The crude product was purified by a standard method to afford trans-dibenzyl cyclopentyl 1,3-dicarboxylate.
With caesium carbonate; In N,N-dimethyl-formamide; at 20℃; for 3.0h;Inert atmosphere;
Step A: (5,5)- dibenzyl cyclopentyl 1,3-dicarboxylate To a mixture of and iraws- cyclopentyl 1 ,3-dicarboxylic acid (1.58 g, 10.0 mmol), Cs2C03 (8.28 g, 25.5 mmol) in DMF (20 mL) was added BnBr (4.36 g, 25.5 mmol). The mixture was stirred at rt under nitrogen for 3 h. The residue was diluted with water and extracted with ethyl acetate. The combined organic solution was washed with water, dried over Na2S04 and concentrated in vacuo. The crude product was purified by a standard method to afford trans- dibenzyl cyclopentyl 1 ,3- dicarboxylate. Chiral SFC separation: cis- and trans- dibenzyl cyclopentyl 1,3-dicarboxylate was separated by chiral SFC to afford (S,S)- dibenzyl cyclohexyl 1 ,3-dicarboxylate. 1H NMR (400 MHz, CHLOROFORM-d) delta 7.43 - 7.34 (m, 10 H), 5.15 (s, 4H), 2.99 - 3.06 (m, 2H), 2.22 (t, / = 7.8 Hz, 2H), 2.1 1 (m, 2H), 1.90 (m, 2H). LC-MS : m/z 171.2 (M-H)~. LC-MS : m/z (M+H) = 423.6
With caesium carbonate; In N,N-dimethyl-formamide; at 20℃; for 3.0h;Inert atmosphere;
Step A: (S,S)- dibenzyl cyclopentyl 1,3-dicarboxylate Bn02C?. (/Gamma<.002Betaeta To a mixture of cis and trans- cyclopentyl 1 ,3-dicarboxylic acid (1.58 g, 10.0 mmol), Cs2C03 (8.28 g, 25.5 mmol) in DMF (20 mL) was added BnBr (4.36 g, 25.5 mmol). The mixture was stirred at rt under nitrogen for 3 h. The residue was diluted with water and extracted with ethyl acetate. The combined organic solution was washed with water, dried over Na2SC>4 and concentrated in vacuo. The crude product was purified by a standard method to afford trans- dibenzyl cyclopentyl 1 ,3- dicarboxylate. Chiral SFC separation: cis- and trans- dibenzyl cyclopentyl 1 ,3-dicarboxylate was separated by chiral SFC to afford (S,S)- dibenzyl cyclohexyl 1 ,3-dicarboxylate. NMR (400 MHz, CHLOROFORM-d) delta 7.43 - 7.34 (m, 10 H), 5.15 (s, 4H), 2.99 - 3.06 (m, 2H), 2.22 (t, J = 7.8 Hz, 2H), 2.1 1 (m, 2H), 1.90 (m, 2H). LC- MS : m/z 171.2 (M-H)~. LC-MS : m/z (M+H) = 423.6
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In dichloromethane; at 20℃;
[000530j A mixture of <strong>[4056-78-4]cyclopentane-1,3-dicarboxylic acid</strong> (124 mg, 0.78 mmol), EDCI (227 mg, 1.18 mmol), HOBt (161 mg, 1.18 mmol), Compound 38A (100 mg, 0.78 mmol) in DCM (20 mL) was stirred at room temperature overnight. After addition of water, the mixture was extracted with DCM (50 mL x 2), washed with brine (50 mL), dried over Na2SO4, and concentrated to render a crude Compound 38B. LC-MS (mlz): 268 [M+1].
A stirred solution of cyclopentane-l,3-dicarboxylic acid (20 g, 0.13 mol, 1 : 1 cis : trans) in 100 mL SOCl2 was heated to reflux overnight. The mixture was cooled, concentrated and used in the next step without further purification. To Nu,Omicron-dimethylhydroxylamine hydrochloride(34 g, 0.36 mol) in CH2CI2 was added DIPEA (45 g, 0.36 mol) followed by cyclopentane-l,3-dicarbonyl dichloride prepared above in CH2CI2 drop wise at 0C. The mixture was stirred at room temperature overnight. It was treated with saturated aqueous NaHC03, then the organic layer was washed with brine and dried over Na2S04 and the solvent was evaporated. The residue was purified by flash chromatography to provide the desired product (20 g, 65%). 1H NMR (400 MHz, CDC13) Cis delta: 3.68 (s, 6H), 3.17 (s, 6H), 3.10 (m, 2H), 2.10 (m, 1H), 1.95 (m, 3H), 1.83 (m, 2H). Trans delta: 3.68 (s, 6H), 3.32 (m, 2H), 3.17 (s, 6H), 2.07 (t, J = 8 Hz, 2H), 2.00 (m, 2H), 1.79 (m, 2H). LC-MS: m/z (M+H) = 245.2
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