* 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 trichlorophosphate In ISOPROPYLAMIDE; acetonitrile at 5 - 20℃;
To a cooled (5°C) solution of (1Z)-1-(2,4-dihydroxyphenyl)ethanone oxime (9.7 g, 57.7 mmol) in acetonitrile (65 mL) and dimethylacetamide (11 mL) was added phosphorus oxychloride (5.6 mL, 60.3 mmol) drop wise. The temperature was not allowed to exceed 10°C during the addition. After 1 hrs stirring at room temperature the yellow slurry was poured on a mixture of sodium hydrogen carbonate and ice. The resulting precipitate was filtered off and dried yielding 6.3 g (73percent) the titled compound.
Stage #1: With hydroxylamine hydrochloride In pyridine at 20℃; for 20.25 h; Stage #2: With trichlorophosphate In ISOPROPYLAMIDE; acetonitrile at 5 - 20℃;
To a stirred solution of 1-(2,4-dihydroxyphenyl)ethanone (20 g, 131 mmol) in pyridine (80 mL) hydroxylamine hydrochloride (9.1 g, 131 mmol) was added over a period of 15 min in small portions at room temperature. The reaction mixture was stirred for 20 h and then diluted with water (600 mL) and extracted with ethyl acetate (2 x 250 mL). The combined organic extracts were washed with water (2 x 250 mL) and 5 percent aqueous HCI (250 mL). The solvent was removed in vacuo. Water (200 mL) was addded to the residue and then concentrated in vacuo, then toluene (200 mL) was added and concentrated in vacuo. The residue was dissolved in a mixture of acetonitrile (150 mL) and dimethylacetamide (25 mL). The solution was cooled to 5°C, phosphorus oxychloride (20.4 g, 12.2 mL, 133 mmol) was added dropwise allowing the temperature to exceed 10°C. After the addition was complete, the reaction mixture was stirred at room temperature for 1 h and then it was slowly poured into a mixture of sodium carbonate (55 g) and ice (ca 800 g). After the ice melted, the resulting slurry was filtered and the solid collected was washed with water (2 x 150 mL). The product was dried in vacuo to afford a yellow powder (14.4 g, 97 mmol, 76percent). 1H-NMR (400 MHz, DMSO-d6): δ 9.68 (br. s, 1H), 7.38 (d, J = 8.5 Hz, 1H), 6.94 (d, J = 2.2 Hz, 1H), 6.74 (dd, J = 8.5, 2.2 Hz, 1H), 2.50 (s, 3H).
Reference：
[1] Journal of Organic Chemistry, 2015, vol. 80, # 17, p. 8657 - 8667
[2] Patent: WO2004/5295, 2004, A1, . Location in patent: Page 80-81
[3] Annali di Chimica (Rome, Italy), 1958, vol. 48, p. 1329,1332, 1333
3
[ 6134-79-8 ]
[ 5078-07-9 ]
Yield
Reaction Conditions
Operation in experiment
63%
With trichlorophosphate In N,N-dimethyl acetamide; acetonitrile at 0 - 20℃; for 1 h;
Compound 5 (5.2 g, 31.1 mmol) was dissolved in DMA/MeCN (6 mL/18 mL), cooled to 0° C. POCl3(5.2 g, 34.2 mmol) was added dropwise to keep the inner temperature below 10° C., then stirred at RT for 1 h. The reaction was monitored by TLC. The reaction mixture was poured into crush-ice (200 mL) containing NaOAc (7.5 g, 91.4 mmol), stirred for 5 min, then stand for 30 min. The precipitate was collected by filtration, dried, afforded compound 6 (2.9 g, 63percent).
Reference：
[1] Synlett, 2008, # 9, p. 1391 - 1393
[2] Patent: JP2015/214548, 2015, A, . Location in patent: Paragraph 1374; 1376; 1377
[3] Synthetic Communications, 1995, vol. 25, # 21, p. 3315 - 3321
[4] Patent: WO2007/90068, 2007, A2, . Location in patent: Page/Page column 92
4
[ 34781-86-7 ]
[ 75-36-5 ]
[ 5078-07-9 ]
Reference：
[1] Patent: US6130217, 2000, A,
5
[ 89-84-9 ]
[ 6134-79-8 ]
[ 5078-07-9 ]
Reference：
[1] Patent: US4310693, 1982, A,
6
[ 2735-04-8 ]
[ 5078-07-9 ]
Reference：
[1] Synthesis, 2003, # 9, p. 1373 - 1376
With trifluorormethanesulfonic acid; trimethylsilylazide In dichloromethane at 20℃;
76%
Stage #1: 2',4'-dihydroxy-4-acetophenone With hydroxylamine hydrochloride In pyridine at 20℃; for 20.25h;
Stage #2: With trichlorophosphate In ISOPROPYLAMIDE; acetonitrile at 5 - 20℃;
9.I Example 9; N-(2-[(2S)-3-(5-Chloro-1'H,3H-spiro[1-benzofuran-2,4'-piperidin]-1'-yl)-2-hydroxy-2-methylpropyl]oxy}-4-hydroxyphenyl)acetamide trifluoroacetate; Step I:; 2-Methyl-1,3-benzoxazol-6-ol
To a stirred solution of 1-(2,4-dihydroxyphenyl)ethanone (20 g, 131 mmol) in pyridine (80 mL) hydroxylamine hydrochloride (9.1 g, 131 mmol) was added over a period of 15 min in small portions at room temperature. The reaction mixture was stirred for 20 h and then diluted with water (600 mL) and extracted with ethyl acetate (2 x 250 mL). The combined organic extracts were washed with water (2 x 250 mL) and 5 % aqueous HCI (250 mL). The solvent was removed in vacuo. Water (200 mL) was addded to the residue and then concentrated in vacuo, then toluene (200 mL) was added and concentrated in vacuo. The residue was dissolved in a mixture of acetonitrile (150 mL) and dimethylacetamide (25 mL). The solution was cooled to 5°C, phosphorus oxychloride (20.4 g, 12.2 mL, 133 mmol) was added dropwise allowing the temperature to exceed 10°C. After the addition was complete, the reaction mixture was stirred at room temperature for 1 h and then it was slowly poured into a mixture of sodium carbonate (55 g) and ice (ca 800 g). After the ice melted, the resulting slurry was filtered and the solid collected was washed with water (2 x 150 mL). The product was dried in vacuo to afford a yellow powder (14.4 g, 97 mmol, 76%). 1H-NMR (400 MHz, DMSO-d6): δ 9.68 (br. s, 1H), 7.38 (d, J = 8.5 Hz, 1H), 6.94 (d, J = 2.2 Hz, 1H), 6.74 (dd, J = 8.5, 2.2 Hz, 1H), 2.50 (s, 3H).
With pyridinium p-toluenesulfonate; triethylamine; In ethyl acetate;
PREPARATION 34 2-Methyl-benzoxazol-6-ol 4-Aminoresorcinol hydrochloride (2.0 g, 12.4 mM), acetyl chloride (1.0 g, 12.6 mM), triethylamine (1.38 g, 13.6 mM) and pyridinium-p-toluenesulfonate (PPTS, 800 mg, 3.2 mM) were refluxed in xylenes (50 mL) for about 18 hours. Additional PPTS (300 mg) was added and the mixture was then refluxed about 48 hours. The reaction mixture was concentrated and the residue dissolved in ethyl acetate (200 mL) and washed with H2 O (3*150 mL). The combined aqueous layer was back extracted with ethyl acetate (200 mL) and the combined organic layers were dried over MgSO4. Filtration and concentration provided 1.36 g. Filtration through a silica gel column eluted with 10% methanol/methylene chloride provided an orange solid, 0.3 g; m.p., 94-96 C.
With triphenylphosphine; diethylazodicarboxylate; In tetrahydrofuran; toluene; at 20℃;Cooling with ice;
To tetrahydrofuran solution (40 ml) of 4 (1.74 g, 11.67 mmol), 14 (2.05 g, 14.00 mmol) and triphenylphosphine (3.68 g, 14.00 mmol) were added, and 40percent diethyl azodicarboxylate/toluene solution (6.11 g, 14.00 mmol) was dropped while ice-cooling with shaking, and the mixture was stirred at room temperature for 3 days. The reaction mixture was evaporated to dryness under reduced pressure, and the residue was purified by silica gel column chromatography (solvent: ethyl acetate/n-hexane = 4/1), to obtain 30 (2.80 g, 87percent) of colorless solid substance. APCI-MS m/z 278[M+H]+
Chemistry
Pharmaceutical Intermediates
Inhibitors/Agonists
Material Science
For Research Only
110K+ Compounds
Competitive Price
1-2 Day Shipping
