tetradecanoic acid

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:140.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A three liter flask equipped with a stirrer, theremometer, nitrogen inlet, Barrett trap and condenser was used. Myristic acid (commercially available from Emery Chemicals, 97 percent purity, 685 grams, 3.0 moles), aniline (300 ml., 3.2 moles) and 120 ml xylene were charged to the flask. The mixture was stirred and heated for approximately 61/2 hours at a temperature of from about 170° C.-220° C. The reaction was conducted in a nitrogen atmosphere. The reaction mixture was then cooled to 140° C. and poured into a 4 liter beaker. About 1.8 liters of denatured alcohol were slowly added to the reaction solution. After standing overnight, the slurry of semi-solid myristanilide was collected by filtration. The filter cake was washed thoroughly with two portions of denatured alcohol and then air dried at about 22° C. The resultant white crystalline solid weighed 706 grams and had a melting point of 83.5° C.-84.5° C. A three liter flask equipped with a stirrer nitrogen inlet, Barrett trap and condenser was used heated for approximately 61/2 hours at a temperature of from about 170° C.-220° C poured into a 4 liter beaker the slurry of semi-solid myristanilide was collected by filtration The filter cake was washed thoroughly with two portions of denatured alcohol air dried at about 22° C

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

Procedure: 4-Iodo-2-oxo-1,2-dihydropyridine-3-carbaldehyde (16.0 g, 64.3 mmol), 4-fluorophenylboronic acid (26.8 g, 193 mmol, Aldrich), copper(II) acetate (23.4 g, 129 mmol, Aldrich), and myristic acid (58.7 g, 257 mmol, Aldrich) were stirred together in 800 mL of toluene. To this solution was added 2,6-lutidine (60 mL, 514 mmol, Aldrich) and the reaction was stirred vigorously for 1 day. An additional 5 g of 4-fluorophenylboronic acid was added and the reaction was stirred vigorously for an additional 3 days. The reaction mixture was concentrated in vacuo and the resulting material was suspended in 10% methanol/ethyl acetate. Celite® was added and the mixture was stirred for 5 minutes. Next the mixture was filtered through a plug of Celite®, concentrated in vacuo, and the resulting material was suspended in ethyl acetate and water. The mixture was filtered through Celite® again to remove additional copper that had precipitated out, washing well with ethyl acetate. The filtrate was washed with 1N aqueous HCl, dried over sodium sulfate, filtered, and concentrated under vacuum. The resulting solid was triturated with ethyl acetate to yield 9.25 g (42%) of 1-(4-fluorophenyl)-4-iodo-2-oxo-1,2-dihydropyridine-3-carbaldehyde as a yellow solid. The filtrate was concentrated in vacuo and the remaining solid was triturated again with ethyl acetate to yield an additional 5.75 g (68% total yield) of the desired product as a yellow solid. 1H NMR (DMSO-d6) δ 9.57 (s, 1H), 7.68 (d, 1H, J=7.2 Hz), 7.58-7.54 (m, 2H), 7.40 (t, 2H, J=8.8 Hz), 7.02 (d, 1H, J=7.2 Hz); MS (ESI+) m/z 344.13 (M+H)+. the reaction was stirred vigorously for an additional 3 days The reaction mixture was concentrated in vacuo Celite® was added the mixture was stirred for 5 minutes Next the mixture was filtered through a plug of Celite® concentrated in vacuo The mixture was filtered through Celite® again to remove additional copper that had precipitated out washing well with ethyl acetate The filtrate was washed with 1N aqueous HCl dried over sodium sulfate filtered concentrated under vacuum The resulting solid was triturated with ethyl acetate

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

Procedure: N-[2-(2-hydroxyethyl)aminoethyl]octadecanamide and N-[2-(2-hydroxyethyl)aminoethyl]pentanamide have been obtained as hydrolysis products from the corresponding imidazolines by Harnsberger and Riebsomer, J. Hetero. Chem. 1, 188 (1964); Gabriel, J. Amer. Oil Chem. Soc., 61, 965 (1984), has described the formation of N-(2-aminoethyl)-N-(2-hydroxyethyl)dodecanamide and N-[2-(2-hydroxyethyl)aminoethyl]dodecanamide as kinetically and thermodynamically controlled products respectively from reaction of N-(2-aminoethyl)aminoethanol and methyl laurate in the presence of catalytic amount of sodium methoxide; Horibatake et al., Jpn. Kokai Tokkyo Koho JP 62,132,946, 16 Jun 1987; C.A. 108, 22881p (1988) claim acylaminoalkyl aminoalkanols, for example, N-[2-(2-hydroxy- ethyl)aminoethyl]dodecanamide, as antistatic agents for synthetic resins; Higuchi and Takahashi, Jpn. Kokai Tokkyo Koho JP 62 57,491, 13 Mar. 1987; C.A. 107, 178711y (1987) claim N-[2-(2-hydroxyethyl) aminoethyl]dodecanamide as being essential in a detergent composition useful for cleaning machines; Moriguchi, Jpn. Kokai Tokkyo Koho JP 62,104,842, 15 May 1987; C.A. 107, 177783m (1987) mentions compositions containing acylaminoalkyleneamines and aminoalcohols as antitack agents for unvulcanized rubbers; Higuchi and Takahashi, Jpn. Kokai Tokkyo Koho JP 61,114,726, 02 Jun 1986; C.A. 105, 155513e (1986) mention the use of N-[2-(2-hydroxyethyl) aminoethyl]dodecanamide and octadec-9-enamide and N-(2-aminoethyl)-N-(2-hydroxyethyl)dodecanamide as emulsifying agents for stable emulsions; Moriguchi, Jpn. Kokai Tokyo Koho JP 71 09,939, 13 Mar 1971; C.A. 76, 60500s (1972) describe the use of N-[2-(2-Hydroxyethyl)aminoethyl]dodecanamide and octadecanamide as heat and water resistant antistatic agents; N-2-aminoethylamides of lower carboxylic acids have been reported by Rosenmund, U.S. Pat. No. 1,926,015 (Sep. 5, 1933); dodecanoic and tetradecanoic acid derivatives (m.p. 51°-2° C. and 62° C.) have been synthesized by Weiner, U.S. Pat. No. 2,387,201 (Oct. 16, 1945) and the latter (m.p. 150°-152° C.) by Kyrides, U.S. Pat. No. 2,399,601 (Apr. 30, 1946), but purity of these compounds is questionable based on the discrepancy in the reported melting points; Harnsberger and Riebsomer have isolated N-[2-(2-hydroxyethyl)aminoethyl]octadecanamide and pentanamide as hydrolysis products from the corresponding imidazolines. as heat

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

Procedure: As described in Preparation 4, with tetradecanoic acid (151 mg, 0.66 mmol), TOTU (67 mg, 0.66 mmol), and N-methylmorpholine (67, 0.66 mmol) in abs. DMF (3 ml; 1 h). Deblocking of 7 (584 mg, 0.6 mmol) with 3% piperidine in abs. DMF (6 ml; 10 min) and addition of above-mentioned soln. (r.t., 2.5 h). Workup with CHCl3 (150 ml) and NaHCO3 soln. (2×70 ml) and reextraction. Purification by FC (silica gel, 12×3 cm, CHCl3, then CHCl3/MeOH 98:2,95:5): 405 mg (70%) of 14. Colorless oil. 1H-NMR (CDCl3): 8.73-8.15 (m, H—C(8), H—C(2), 4 H o to NO2, NH(ade)); 7.47-7.38 (m, 4H m to NO2); 6.12 (d, H—C(1′)); 5.73 (m, H—C(2′)); 5.57 (t, NH(CH2)5CO); 4.68 (m, H—C(4′)); 4.54, 4.43 (2t, 2 OCH2CH2); 4.4-4.2 (m, 2 H—C(5′)); 3.7-3.5 (m, 1 CH2 of NH(CH2)5CO); 3.25-3.1 (m, 2 OCH2CH2, 1 CH2 of NH(CH2)5CO); 2.65, 2.25 (2m, 2 H—C(3′)); 2.27, 2.15 (2t, 2 CH2 of NH(CH2)5CO), 1 CH2 of Me(CH2)12CO); 1.7-1.15 (m, 3 CH2 of NH(CH2)5CO), 11 CH2 of Me(CH2)12CO); 0.87 (t, Me(CH2)12CO). (r.t., 2.5 h) Purification by FC (silica gel, 12×3 cm, CHCl3

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

Procedure: As described in Preparation 4, with tetradecanoic acid (151 mg, 0.66 mmol), TOTU (67 mg, 0.66 mmol), and N-methylmorpholine (67, 0.66 mmol) in abs. DMF (3 ml; 1 h). Deblocking of 7 (584 mg, 0.6 mmol) with 3% piperidine in abs. DMF (6 ml; 10 min) and addition of above-mentioned soln. (r.t., 2.5 h). Workup with CHCl3 (150 ml) and NaHCO3 soln. (2×70 ml) and reextraction. Purification by FC (silica gel, 12×3 cm, CHCl3, then CHCl3/MeOH 98:2,95:5): 405 mg (70%) of 14. Colorless oil. 1H-NMR (CDCl3): 8.73-8.15 (m, H—C(8), H—C(2), 4 H o to NO2, NH(ade)); 7.47-7.38 (m, 4H m to NO2); 6.12 (d, H—C(1′)); 5.73 (m, H—C(2′)); 5.57 (t, NH(CH2)5CO); 4.68 (m, H—C(4′)); 4.54, 4.43 (2t, 2 OCH2CH2); 4.4-4.2 (m, 2 H—C(5′)); 3.7-3.5 (m, 1 CH2 of NH(CH2)5CO); 3.25-3.1 (m, 2 OCH2CH2, 1 CH2 of NH(CH2)5CO); 2.65, 2.25 (2m, 2 H—C(3′)); 2.27, 2.15 (2t, 2 CH2 of NH(CH2)5CO), 1 CH2 of Me(CH2)12CO); 1.7-1.15 (m, 3 CH2 of NH(CH2)5CO), 11 CH2 of Me(CH2)12CO); 0.87 (t, Me(CH2)12CO). (r.t., 2.5 h) Purification by FC (silica gel, 12×3 cm, CHCl3

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

Procedure: Cadmium nitrate (5 mmol) was dissolved in anhydrous methanol (50 mL). A sodium-myristate solution was prepared by dissolving sodium hydroxide (15 mmol) and myristic acid (15 mmol) in anhydrous methanol (500 mL). Then the cadmium-nitrate solution was added dropwise (one drop per second) into the sodium-myristate solution with vigorous stirring. The resulting white precipitate was washed with methanol three times, and then dried at ˜60° C. under vacuum overnight. The resulting white precipitate was washed with methanol three times dried at ˜60° C. under vacuum overnight

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

Procedure: 4-Iodo-2-oxo-1,2-dihydropyridine-3-carbaldehyde (12.0 g, 48.3 mmol), 4-fluorophenylboronic acid (20.1 g, 144.7 mmol), copper(II) acetate (17.55 g, 96.75 mmol), and myristic acid (44 g, 193 mmol) were combined in toluene (700 mL), treated 2,6-lutidine (45 mL, 385 mmol), and stirred vigorously for 1 day. Additional 4-fluorophenylboronic acid (5 g) was added and the reaction was stirred vigorously for an additional 3 days. The reaction mixture was concentrated and then suspended in 10% methanol/EtOAc. Diatomaceous earth was added and the mixture was stirred for 5 minutes. The mixture was filtered through a plug of diatomaceous earth. The filtrate was concentrated, and suspended in EtOAc and water. The mixture was again filtered through diatomaceous earth, rinsing forward with EtOAc. The filtrate was washed with 1N HCl, dried over Na2SO4, and concentrated under vacuum. The resulting solid was triturated with EtOAc to yield 1-(4-fluorophenyl)-4-iodo-2-oxo-1,2-dihydropyridine-3-carbaldehyde (8.0 g, 42% yield) as a yellow solid. the reaction was stirred vigorously for an additional 3 days The reaction mixture was concentrated Diatomaceous earth was added the mixture was stirred for 5 minutes The mixture was filtered through a plug of diatomaceous earth The filtrate was concentrated The mixture was again filtered through diatomaceous earth rinsing forward with EtOAc The filtrate was washed with 1N HCl dried over Na2SO4 concentrated under vacuum The resulting solid was triturated with EtOAc

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

Procedure: 4-Iodo-2-oxo-1,2-dihydropyridine-3-carbaldehyde (16.0 g, 64.3 mmol), 4-fluorophenylboronic acid (26.8 g, 193 mmol, Aldrich), copper(II) acetate (23.4 g, 129 mmol, Aldrich), and myristic acid (58.7 g, 257 mmol, Aldrich) were stirred together in 800 mL of toluene. To this solution was added 2,6-lutidine (60 mL, 514 mmol, Aldrich) and the reaction was stirred vigorously for 1 day. An additional 5 g of 4-fluorophenylboronic acid was added and the reaction was stirred vigorously for an additional 3 days. The reaction mixture was concentrated in vacuo and the resulting material was suspended in 10% methanol/ethyl acetate. Celite® was added and the mixture was stirred for 5 minutes. Next the mixture was filtered through a plug of Celite®, concentrated in vacuo, and the resulting material was suspended in ethyl acetate and water. The mixture was filtered through Celite® again to remove additional copper that had precipitated out, washing well with ethyl acetate. The filtrate was washed with 1N aqueous HCl, dried over sodium sulfate, filtered, and concentrated under vacuum. The resulting solid was triturated with ethyl acetate to yield 9.25 g (42%) of 1-(4-fluorophenyl)-4-iodo-2-oxo-1,2-dihydropyridine-3-carbaldehyde as a yellow solid. The filtrate was concentrated in vacuo and the remaining solid was triturated again with ethyl acetate to yield an additional 5.75 g (68% total yield) of the desired product as a yellow solid. 1H NMR (DMSO-d6) δ 9.57 (s, 1H), 7.68 (d, 1H, J=7.2 Hz), 7.58-7.54 (m, 2H), 7.40 (t, 2H, J=8.8 Hz), 7.02 (d, 1H, J=7.2 Hz); MS (ESI+) m/z 344.13 (M+H)+. the reaction was stirred vigorously for an additional 3 days The reaction mixture was concentrated in vacuo Celite® was added the mixture was stirred for 5 minutes Next the mixture was filtered through a plug of Celite® concentrated in vacuo The mixture was filtered through Celite® again to remove additional copper that had precipitated out washing well with ethyl acetate The filtrate was washed with 1N aqueous HCl dried over sodium sulfate filtered concentrated under vacuum The resulting solid was triturated with ethyl acetate

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

Procedure: 4-Iodo-2-oxo-1,2-dihydropyridine-3-carbaldehyde (16.0 g, 64.3 mmol), 4-fluorophenylboronic acid (26.8 g, 193 mmol, Aldrich), copper(II) acetate (23.4 g, 129 mmol, Aldrich), and myristic acid (58.7 g, 257 mmol, Aldrich) were stirred together in 800 mL of toluene. To this solution was added 2,6-lutidine (60 mL, 514 mmol, Aldrich) and the reaction was stirred vigorously for 1 day. An additional 5 g of 4-fluorophenylboronic acid was added and the reaction was stirred vigorously for an additional 3 days. The reaction mixture was concentrated in vacuo and the resulting material was suspended in 10% methanol/ethyl acetate. Celite® was added and the mixture was stirred for 5 minutes. Next the mixture was filtered through a plug of Celite®, concentrated in vacuo, and the resulting material was suspended in ethyl acetate and water. The mixture was filtered through Celite® again to remove additional copper that had precipitated out, washing well with ethyl acetate. The filtrate was washed with 1N aqueous HCl, dried over sodium sulfate, filtered, and concentrated under vacuum. The resulting solid was triturated with ethyl acetate to yield 9.25 g (42%) of 1-(4-fluorophenyl)-4-iodo-2-oxo-1,2-dihydropyridine-3-carbaldehyde as a yellow solid. The filtrate was concentrated in vacuo and the remaining solid was triturated again with ethyl acetate to yield an additional 5.75 g (68% total yield) of the desired product as a yellow solid. 1H NMR (DMSO-d6) δ 9.57 (s, 1H), 7.68 (d, 1H, J=7.2 Hz), 7.58-7.54 (m, 2H), 7.40 (t, 2H, J=8.8 Hz), 7.02 (d, 1H, J=7.2 Hz); MS (ESI+) m/z 344.13 (M+H)+. the reaction was stirred vigorously for an additional 3 days The reaction mixture was concentrated in vacuo Celite® was added the mixture was stirred for 5 minutes Next the mixture was filtered through a plug of Celite® concentrated in vacuo The mixture was filtered through Celite® again to remove additional copper that had precipitated out washing well with ethyl acetate The filtrate was washed with 1N aqueous HCl dried over sodium sulfate filtered concentrated under vacuum The resulting solid was triturated with ethyl acetate

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

Procedure: Myristoyl chloride was synthesized by refluxing myristic acid (7.0 g) and thionyl chloride (9 ml) in trichloroethylene (100 ml) for 3 h. The solvent was then evaporated. The solvent was then evaporated

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

Procedure: Phenylboronic acid (0.16 g, 0.81 mmol), Cu(OAc)2 (0.049 g, 0.27 mmol), and myristic acid (0.037 g, 0.16 mmol) were combined in a 100-mL round-bottom flask with a large stir bar. A rubber septum was attached, and dry toluene (2 mL), 2,6-lutidine (0.066 mL, 0.57 mmol), and 1-(4-amino-benzyl)-3-phenyl-1H-indole indolecarboxylic acid ethyl ester (0.20 g, 0.54 mmol) were successively added. The resulting mixture was stirred at a high rate for 24 h, diluted with ethyl acetate (10 mL), filtered through a plug of silica gel, and then purified by column chromatography (5 to 25% EtOAc/hexanes) to give a gummy solid. To a stirred solution of the gummy solid in 15 mL of 2:1:1 THF/MeOH/water was added lithium hydroxide monohydrate (0.1 g, 2.4 mmol). The reaction was stirred at 40° C. for 5 h. Most of the organic solvents was removed and the reaction mixture was made acidic (pH 6) with glacial acetic acid, and the solid was collected and purified by HPLC as a white powder (0.023 g, 10%): 1H NMR (DMSO-d6) δ 5.64 (s, 2H), 6.77 (t, J=7.4 Hz, 1H), 6.96 (d, J=8.5 Hz, 2H), 7.00 (dd, J=7.6, 0.9 Hz, 2H), 7.04(t, J=7.1 Hz, 1H), 7.15-7.19(m, 4H), 7.25 (t, J=7.11 Hz, 1H), 7.39 (t, J=7.4 Hz, 2H), 7.46-7.53 (m, 1H), 7.53 (t, J=7.4 Hz, 2H), 7.54-7.56 (m, 2H), 8.08 (br s, 1H), 13.01 (br s, 1H); MS (ESI) m/z 419 (MH+); MS (ESI) m/z 417 ([M−H]−); HRMS calcd for C28H23N2O2: 419.1757; found (ESI+): 419.1755. filtered through a plug of silica gel purified by column chromatography (5 to 25% EtOAc/hexanes) to give a gummy solid The reaction was stirred at 40° C. for 5 h Most of the organic solvents was removed the solid was collected purified by HPLC as a white powder (0.023 g, 10%)