5-iodopent-1-ene

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

Procedure: To a solution of 2-chloro-N-methoxy-N-methylacetamide (6.0 g, 48.8 mmol) in dry DMF (20 mL) at 23° C. was added 3-mercaptophenol (4.44 mL, 48.8 mmol) and K2CO3 (6.7 g, 48.8 mmol). The resulting suspension was stirred at 23° C. overnight. After this period of time, Merrifield resin (24 g, <2 mmol.g−1, <48.8 mmol) was added to the mixture followed by K2CO3 (11.4 g, 83.0 mmol) as well as TBAI (catalytic amount), and the suspension was heated up to 50° C. After 12 hours at this temperature, the resin was filtered and washed several times: HClaq. (50 mL), MeOH (50 mL), CH2Cl2 (50 mL) and Et2O (50 mL). The resin was dried under reduced pressure to constant mass of 29.2 g. The final mass gain (5.2 g, 27.3 mmol) indicated an estimate loading of 0.81 mmol.g−1. Resin 2-49 (10 g, 0.81 mmol.g−1) was suspended in a 1:1 mixture of HFIP/CH2Cl2 (50 mL). To this suspension, H2O2 (3 mL, 16.0 mmol) was added at 23° C. and the resulting mixture was shaken for 12 h. Resin 2-113 was then filtered, washed using MeOH (50 mL), CH2Cl2 (50 mL) and Et2O (50 mL) and dried under reduced pressure to constant mass before subsequent use. Resin 2-113 (4.0 g, <0.81 mmol.g−1) was suspended in DMSO (40 mL) followed by the addition of tBuOK (336 mg, 3.0 mmol). After shaking the reaction for 1 h at room temperature, 5-iodo-1-pentene (588 mg, 3.0 mmol) was added to the suspension and the mixture was shaken for 3 h. The resin was filtered, washed and dried as before. Then, it was suspended in toluene and heated at 80° C. After 8 h at this temperature, the resin was filtered and washed several times with more toluene. The combined toluene solutions were evaporated giving pure compound 2-114 as a colourless oil (321 mg, 77%) of 95% purity judged by NMR. 1H NMR (400 MHz, CDCl3, 25° C.): δ=6.94 (dt, J=15.7, 6.7 Hz, 1H), 6.39 (d, J=15.2 Hz, 1H), 5.84-5.74 (m, 1H), 5.02 (dd, J=17.4, 1.7 Hz, 1H), 4.97 (d, J=10.1 Hz, 1H), 3.67 (s, 3H), 3.21 (s, 3H), 2.34-2.29 (m, 2H), 2.23-2.18 (m, 2H); 13C NMR (100 MHz, CDCl3, 25° C.): δ=166.8, 146.7, 137.3, 119.1, 115.3, 61.6, 32.3, 31.7, (one carbon is not detected); I.R. (film): νmax=2934, 1681, 1638, 1378, 1179 cm−1. After this period of time, Merrifield resin (24 g, <2 mmol.g−1, <48.8 mmol) was added to the mixture the suspension was heated up to 50° C After 12 hours at this temperature the resin was filtered washed several times The resin was dried under reduced pressure to constant mass of 29.2 g Resin 2-49 (10 g, 0.81 mmol.g−1) was suspended in a 1:1 mixture of HFIP/CH2Cl2 (50 mL) the resulting mixture was shaken for 12 h Resin 2-113 was then filtered washed dried under reduced pressure to constant mass before subsequent use After shaking the reaction for 1 h at room temperature the mixture was shaken for 3 h The resin was filtered washed dried as before heated at 80° C After 8 h at this temperature the resin was filtered washed several times with more toluene The combined toluene solutions were evaporated

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

Procedure: To a solution of 2-chloro-N-methoxy-N-methylacetamide (6.0 g, 48.8 mmol) in dry DMF (20 mL) at 23° C. was added 3-mercaptophenol (4.44 mL, 48.8 mmol) and K2CO3 (6.7 g, 48.8 mmol). The resulting suspension was stirred at 23° C. overnight. After this period of time, Merrifield resin (24 g, <2 mmol.g−1, <48.8 mmol) was added to the mixture followed by K2CO3 (11.4 g, 83.0 mmol) as well as TBAI (catalytic amount), and the suspension was heated up to 50° C. After 12 hours at this temperature, the resin was filtered and washed several times: HClaq. (50 mL), MeOH (50 mL), CH2Cl2 (50 mL) and Et2O (50 mL). The resin was dried under reduced pressure to constant mass of 29.2 g. The final mass gain (5.2 g, 27.3 mmol) indicated an estimate loading of 0.81 mmol.g−1. Resin 2-49 (10 g, 0.81 mmol.g−1) was suspended in a 1:1 mixture of HFIP/CH2Cl2 (50 mL). To this suspension, H2O2 (3 mL, 16.0 mmol) was added at 23° C. and the resulting mixture was shaken for 12 h. Resin 2-113 was then filtered, washed using MeOH (50 mL), CH2Cl2 (50 mL) and Et2O (50 mL) and dried under reduced pressure to constant mass before subsequent use. Resin 2-113 (4.0 g, <0.81 mmol.g−1) was suspended in DMSO (40 mL) followed by the addition of tBuOK (336 mg, 3.0 mmol). After shaking the reaction for 1 h at room temperature, 5-iodo-1-pentene (588 mg, 3.0 mmol) was added to the suspension and the mixture was shaken for 3 h. The resin was filtered, washed and dried as before. Then, it was suspended in toluene and heated at 80° C. After 8 h at this temperature, the resin was filtered and washed several times with more toluene. The combined toluene solutions were evaporated giving pure compound 2-114 as a colourless oil (321 mg, 77%) of 95% purity judged by NMR. 1H NMR (400 MHz, CDCl3, 25° C.): δ=6.94 (dt, J=15.7, 6.7 Hz, 1H), 6.39 (d, J=15.2 Hz, 1H), 5.84-5.74 (m, 1H), 5.02 (dd, J=17.4, 1.7 Hz, 1H), 4.97 (d, J=10.1 Hz, 1H), 3.67 (s, 3H), 3.21 (s, 3H), 2.34-2.29 (m, 2H), 2.23-2.18 (m, 2H); 13C NMR (100 MHz, CDCl3, 25° C.): δ=166.8, 146.7, 137.3, 119.1, 115.3, 61.6, 32.3, 31.7, (one carbon is not detected); I.R. (film): νmax=2934, 1681, 1638, 1378, 1179 cm−1. After this period of time, Merrifield resin (24 g, <2 mmol.g−1, <48.8 mmol) was added to the mixture the suspension was heated up to 50° C After 12 hours at this temperature the resin was filtered washed several times The resin was dried under reduced pressure to constant mass of 29.2 g Resin 2-49 (10 g, 0.81 mmol.g−1) was suspended in a 1:1 mixture of HFIP/CH2Cl2 (50 mL) the resulting mixture was shaken for 12 h Resin 2-113 was then filtered washed dried under reduced pressure to constant mass before subsequent use After shaking the reaction for 1 h at room temperature the mixture was shaken for 3 h The resin was filtered washed dried as before heated at 80° C After 8 h at this temperature the resin was filtered washed several times with more toluene The combined toluene solutions were evaporated

Conditions: temp:130.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 1H NMR (CDCl3) δ=5.8 (m, 1H), 5.0 (m, 2H), 3.2 (t, 2H), 2.2 (sq, 2H), 1.8 (sq, 2H). Triethyl phosphite (400 mL, 2.3 mol, 3.5 eq.) was added to the 1-iodo-4-pentene, and the mixture was heated to 130° C. for three hours. Diethyl ethyl phosphonate was removed by fractional vacuum distillation, revealing the desired 4-pentenyl phosphonic acid diethyl ester which was used without further purification. 1H NMR (CDCl3) δ=5.7 (m, 1H), 4.8 (m, 2H), 4.0 (m, 4H), 2.0 (sq, 2H), 1.7 (m, 4H), 1.2 (t, 6H). 31P NMR (CDCl3) δ=33.3. Diethyl ethyl phosphonate was removed by fractional vacuum distillation was used without further purification

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

Procedure: Sodium iodide (100.6 g, 0.66 mol, 1.1 eq.) was added to a solution of 1-bromo-4-pentene (100 g, 0.67 mol) in acetone (250 mL) and the mixture was stirred at room temperature overnight. The mixture was filtered and the solid was washed with acetone. The acetone filtrate and the acetone wash were combined. The acetone was then removed by distillation, revealing 1-iodo-4-pentene, which was used in the next step. 1H NMR (CDCl3) δ=5.8 (m, 1H), 5.0 (m, 2H), 3.2 (t, 2H), 2.2 (sq, 2H), 1.8 (sq, 2H). Triethyl phosphite (400 mL, 2.3 mol, 3.5 eq.) was added to the 1-iodo-4-pentene, and the mixture was heated to 130° C. for three hours. Diethyl ethyl phosphonate was removed by fractional vacuum distillation, revealing the desired 4-pentenyl phosphonic acid diethyl ester which was used without further purification. 1H NMR (CDCl3) δ=5.7 (m, 1H), 4.8 (m, 2H), 4.0 (m, 4H), 2.0 (sq, 2H), 1.7 (m, 4H), 1.2 (t, 6H). 31P NMR (CDCl3) δ=33.3. The mixture was filtered the solid was washed with acetone The acetone filtrate and the acetone wash The acetone was then removed by distillation the mixture was heated to 130° C. for three hours Diethyl ethyl phosphonate was removed by fractional vacuum distillation was used without further purification

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

Procedure: Sodium iodide (100.6 g, 0.66 mol, 1.1 eq.) was added to a solution of 1-bromo-4-pentene (100 g, 0.67 mol) in acetone (250 mL) and the mixture was stirred at room temperature overnight. The mixture was filtered and the solid was washed with acetone. The acetone filtrate and the acetone wash were combined. The acetone was then removed by distillation, revealing 1-iodo-4-pentene, which was used in the next step. 1H NMR (CDCl3) δ=5.8 (m, 1H), 5.0 (m, 2H), 3.2 (t, 2H), 2.2 (sq, 2H), 1.8 (sq, 2H). Triethyl phosphite (400 mL, 2.3 mol, 3.5 eq.) was added to the 1-iodo-4-pentene, and the mixture was heated to 130° C. for three hours. Diethyl ethyl phosphonate was removed by fractional vacuum distillation, revealing the desired 4-pentenyl phosphonic acid diethyl ester which was used without further purification. 1H NMR (CDCl3) δ=5.7 (m, 1H), 4.8 (m, 2H), 4.0 (m, 4H), 2.0 (sq, 2H), 1.7 (m, 4H), 1.2 (t, 6H). 31P NMR (CDCl3) δ=33.3. The mixture was filtered the solid was washed with acetone The acetone filtrate and the acetone wash The acetone was then removed by distillation the mixture was heated to 130° C. for three hours Diethyl ethyl phosphonate was removed by fractional vacuum distillation was used without further purification

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

Procedure: To a solution of 2-chloro-N-methoxy-N-methylacetamide (6.0 g, 48.8 mmol) in dry DMF (20 mL) at 23° C. was added 3-mercaptophenol (4.44 mL, 48.8 mmol) and K2CO3 (6.7 g, 48.8 mmol). The resulting suspension was stirred at 23° C. overnight. After this period of time, Merrifield resin (24 g, <2 mmol·g−1, <48.8 mmol) was added to the mixture followed by K2CO3 (11.4 g, 83.0 mmol) as well as TBAI (catalytic amount), and the suspension was heated up to 50° C. After 12 hours at this temperature, the resin was filtered and washed several times: HClaq. (50 mL), MeOH (50 mL), CH2Cl2 (50 mL) and Et2O (50 mL). The resin was dried under reduced pressure to constant mass of 29.2 g. The final mass gain (5.2 g, 27.3 mmol) indicated an estimate loading of 0.81 mmol·g−1. Resin 2-49 (10 g, 0.81 mmol·g−1) was suspended in a 1:1 mixture of HFIP/CH7Cl2 (50 mL). To this suspension, H2O2 (3 mL, 16.0 mmol) was added at 23° C. and the resulting mixture was shaken for 12 h. Resin 2-113 was then filtered, washed using MeOH (50 mL), CH2Cl2 (50 mL) and Et2O (50 mL) and dried under reduced pressure to constant mass before subsequent use. Resin 2-113 (4.0 g, <0.81 mmol·g−1) was suspended in DMSO (40 mL) followed by the addition of tBuOK (336 mg, 3.0 mmol). After shaking the reaction for 1 h at room temperature, 5-iodo-1-pentene (588 mg, 3.0 mmol) was added to the suspension and the mixture was shaken for 3 h. The resin was filtered, washed and dried as before. Then, it was suspended in toluene and heated at 80° C. After 8 h at this temperature, the resin was filtered and washed several times with more toluene. The combined toluene solutions were evaporated giving pure compound 2-114 as a colourless oil (321 mg, 77%) of 95% purity judged by NMR. 1H NMR (400 MHz, CDCl3, 25° C.): δ=6.94 (dt, J=15.7, 6.7 Hz, 1H), 6.39 (d, J=15.2 Hz, 1H), 5.84-5.74 (m, 1H), 5.02 (dd, J=17.4, 1.7 Hz, 1H), 4.97 (d, J=10.1 Hz, 1H), 3.67 (s, 3H), 3.21 (s, 3H), 2.34-2.29 (m, 2H), 2.23-2.18 (m, 2H); 13C NMR (100 MHz, CDCl3, 25° C.): δ=166.8, 146.7, 137.3, 119.1, 115.3, 61.6, 32.3, 31.7, (one carbon is not detected); I.R. (film): νmax=2934, 1681, 1638, 1378, 1179 cm−1. After this period of time, Merrifield resin (24 g, <2 mmol·g−1, <48.8 mmol) was added to the mixture the suspension was heated up to 50° C After 12 hours at this temperature the resin was filtered washed several times The resin was dried under reduced pressure to constant mass of 29.2 g Resin 2-49 (10 g, 0.81 mmol·g−1) was suspended in a 1:1 mixture of HFIP/CH7Cl2 (50 mL) the resulting mixture was shaken for 12 h Resin 2-113 was then filtered washed dried under reduced pressure to constant mass before subsequent use After shaking the reaction for 1 h at room temperature the mixture was shaken for 3 h The resin was filtered washed dried as before heated at 80° C After 8 h at this temperature the resin was filtered washed several times with more toluene The combined toluene solutions were evaporated

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

Procedure: To a solution of 2-chloro-N-methoxy-N-methylacetamide (6.0 g, 48.8 mmol) in dry DMF (20 mL) at 23° C. was added 3-mercaptophenol (4.44 mL, 48.8 mmol) and K2CO3 (6.7 g, 48.8 mmol). The resulting suspension was stirred at 23° C. overnight. After this period of time, Merrifield resin (24 g, <2 mmol·g−1, <48.8 mmol) was added to the mixture followed by K2CO3 (11.4 g, 83.0 mmol) as well as TBAI (catalytic amount), and the suspension was heated up to 50° C. After 12 hours at this temperature, the resin was filtered and washed several times: HClaq. (50 mL), MeOH (50 mL), CH2Cl2 (50 mL) and Et2O (50 mL). The resin was dried under reduced pressure to constant mass of 29.2 g. The final mass gain (5.2 g, 27.3 mmol) indicated an estimate loading of 0.81 mmol·g−1. Resin 2-49 (10 g, 0.81 mmol·g−1) was suspended in a 1:1 mixture of HFIP/CH2Cl2 (50 mL). To this suspension, H2O2 (3 mL, 16.0 mmol) was added at 23° C. and the resulting mixture was shaken for 12 h. Resin 2-113 was then filtered, washed using MeOH (50 mL), CH2Cl2 (50 mL) and Et2O (50 mL) and dried under reduced pressure to constant mass before subsequent use. Resin 2-113 (4.0 g, <0.81 mmol·g−1) was suspended in DMSO (40 mL) followed by the addition of tBuOK (336 mg, 3.0 mmol). After shaking the reaction for 1 h at room temperature, 5-iodo-1-pentene (588 mg, 3.0 mmol) was added to the suspension and the mixture was shaken for 3 h. The resin was filtered, washed and dried as before. Then, it was suspended in toluene and heated at 80° C. After 8 h at this temperature, the resin was filtered and washed several times with more toluene. The combined toluene solutions were evaporated giving pure compound 2-114 as a colourless oil (321 mg, 77%) of 95% purity judged by NMR. 1H NMR (400 MHz, CDCl3, 25° C.): δ=6.94 (dt, J=15.7, 6.7 Hz, 1H), 6.39 (d, J=15.2 Hz, 1H), 5.84-5.74 (m, 1H), 5.02 (dd, J=17.4, 1.7 Hz, 1H), 4.97 (d, J=10.1 Hz, 1H), 3.67 (s, 3H), 3.21 (s, 3H), 2.34-2.29 (m, 2H), 2.23-2.18 (m, 2H); 13C NMR (100 MHz, CDCl3, 25° C.): δ=166.8, 146.7, 137.3, 119.1, 115.3, 61.6, 32.3, 31.7, (one carbon is not detected); I.R. (film): νmax=2934, 1681, 1638, 1378, 1179 cm−1. After this period of time, Merrifield resin (24 g, <2 mmol·g−1, <48.8 mmol) was added to the mixture the suspension was heated up to 50° C After 12 hours at this temperature the resin was filtered washed several times The resin was dried under reduced pressure to constant mass of 29.2 g Resin 2-49 (10 g, 0.81 mmol·g−1) was suspended in a 1:1 mixture of HFIP/CH2Cl2 (50 mL) the resulting mixture was shaken for 12 h Resin 2-113 was then filtered washed dried under reduced pressure to constant mass before subsequent use After shaking the reaction for 1 h at room temperature the mixture was shaken for 3 h The resin was filtered washed dried as before heated at 80° C After 8 h at this temperature the resin was filtered washed several times with more toluene The combined toluene solutions were evaporated

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

Procedure: A procedure previously described for dialkylation of N-(diphenylmethylene)glycine ethyl ester was used after modifications (see Denmark, S. E.; Stavenger, R. A.; Faucher, A.-M.; Edwards, J. P. J. Org. Chem. 1997, 62, 3375-3389): To a stirred solution of N-(diphenylmethylene)glycine ethyl ester 10 (13.63 g, 51 mmol) in THF (250 mL) was added a solution of KHMDS (11.2 g, 56.1 mmol, 1.1 equiv.) in THF (56 mL) via a cannula at −78° C. over 15 min. After stirring at −78° C. for 1 h, the resulting orange-colored solution was treated with 5-iodo-1-pentene (12 g, 61.2 mmol, 1.2 equiv.). The reaction mixture was allowed to warm to room temperature and stirred for 2 h. The resulting suspension was cooled to −40° C. and another solution of KHMDS (15.3 g, 76.5 mmol, 1.5 equiv.) in THF (77 mL) was added via a cannula over 15 min and stirred for 1 h. 5-iodo-1-pentene (16 g, 81.6 mmol, 1.6 equiv.) was then quickly added to the burgundy-colored mixture, and the reaction was left to warm to room temperature overnight (16 h). The reaction was quenched by addition of saturated NH4Cl solution in water (100 mL). The organics were extracted with ethyl acetate (2×150 mL), washed with Na2S2O3 solution and then with brine. The organic layer was dried over MgSO4, filtered, and concentrated under reduced pressure. The resulting residue was dried in vacuo overnight and used for the next reaction without further purification: 1H-NMR (400 MHz, CDCl3) δ 7.83-7.12 (m, 10H), 5.80 (m, 2H), 5.02 (dd, J=17.2, 1.6 Hz, 2H), 4.96 (dd, J=10.4, 1.6 Hz, 2H), 3.74 (q, J=6.8 Hz, 2H), 2.05 (dd, J=14.0, 7.2 Hz, 4H), 1.92 (m, 4H), 1.45 (m, 4H), 1.13 (t, J=6.8 Hz, 3H); 13C-NMR (100 MHz, CDCl3) δ 174.8, 166.0, 141.3, 138.9, 128.5, 128.2, 127.9, 115.0, 69.2, 60.5, 37.5, 34.4, 23.3, 14.2; HRMS (ESI) m/z for C27H34NO2 [M+H]+ calcd 404.2589. found 404.2577. to warm to room temperature stirred for 2 h The resulting suspension was cooled to −40° C. stirred for 1 h the reaction was left to warm to room temperature overnight (16 h) The reaction was quenched by addition of saturated NH4Cl solution in water (100 mL) The organics were extracted with ethyl acetate (2×150 mL) washed with Na2S2O3 solution The organic layer was dried over MgSO4 filtered concentrated under reduced pressure The resulting residue was dried in vacuo overnight used for the next reaction without further purification

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

Procedure: To a solution of 2-chloro-N-methoxy-N-methylacetamide (6.0 g, 48.8 mmol) in dry DMF (20 mL) at 23° C. was added 3-mercaptophenol (4.44 mL, 48.8 mmol) and K2CO3 (6.7 g, 48.8 mmol). The resulting suspension was stirred at 23° C. overnight. After this period of time, Merrifield resin (24 g, <2 mmol.g−1, <48.8 mmol) was added to the mixture followed by K2CO3 (11.4 g, 83.0 mmol) as well as TBAI (catalytic amount), and the suspension was heated up to 50° C. After 12 hours at this temperature, the resin was filtered and washed several times: HClaq. (50 mL), MeOH (50 mL), CH2Cl2 (50 mL) and Et2O (50 mL). The resin was dried under reduced pressure to constant mass of 29.2 g. The final mass gain (5.2 g, 27.3 mmol) indicated an estimate loading of 0.81 mmol.g−1. Resin 2-49 (10 g, 0.81 mmol.g−1) was suspended in a 1:1 mixture of HFIP/CH2Cl2 (50 mL). To this suspension, H2O2 (3 mL, 16.0 mmol) was added at 23° C. and the resulting mixture was shaken for 12 h. Resin 2-113 was then filtered, washed using MeOH (50 mL), CH2Cl2 (50 mL) and Et2O (50 mL) and dried under reduced pressure to constant mass before subsequent use. Resin 2-113 (4.0 g, <0.81 mmol.g−1) was suspended in DMSO (40 mL) followed by the addition of tBuOK (336 mg, 3.0 mmol). After shaking the reaction for 1 h at room temperature, 5-iodo-1-pentene (588 mg, 3.0 mmol) was added to the suspension and the mixture was shaken for 3 h. The resin was filtered, washed and dried as before. Then, it was suspended in toluene and heated at 80° C. After 8 h at this temperature, the resin was filtered and washed several times with more toluene. The combined toluene solutions were evaporated giving pure compound 2-114 as a colourless oil (321 mg, 77%) of 95% purity judged by NMR. 1H NMR (400 MHz, CDCl3, 25° C.): δ=6.94 (dt, J=15.7, 6.7 Hz, 1H), 6.39 (d, J=15.2 Hz, 1H), 5.84-5.74 (m, 1H), 5.02 (dd, J=17.4, 1.7 Hz, 1H), 4.97 (d, J=10.1 Hz, 1H), 3.67 (s, 3H), 3.21 (s, 3H), 2.34-2.29 (m, 2H), 2.23-2.18 (m, 2H); 13C NMR (100 MHz, CDCl3, 25° C.): δ=166.8, 146.7, 137.3, 119.1, 115.3, 61.6, 32.3, 31.7, (one carbon is not detected); I.R. (film): νmax=2934, 1681, 1638, 1378, 1179 cm−1. After this period of time, Merrifield resin (24 g, <2 mmol.g−1, <48.8 mmol) was added to the mixture the suspension was heated up to 50° C After 12 hours at this temperature the resin was filtered washed several times The resin was dried under reduced pressure to constant mass of 29.2 g Resin 2-49 (10 g, 0.81 mmol.g−1) was suspended in a 1:1 mixture of HFIP/CH2Cl2 (50 mL) the resulting mixture was shaken for 12 h Resin 2-113 was then filtered washed dried under reduced pressure to constant mass before subsequent use After shaking the reaction for 1 h at room temperature the mixture was shaken for 3 h The resin was filtered washed dried as before heated at 80° C After 8 h at this temperature the resin was filtered washed several times with more toluene The combined toluene solutions were evaporated