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Chemical Structure| 136663-23-5 Chemical Structure| 136663-23-5
Chemical Structure| 136663-23-5

Methyl 2-methylbenzo[d]oxazole-6-carboxylate

CAS No.: 136663-23-5

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Cat. No.: A201411 Purity: 98%

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Product Details of [ 136663-23-5 ]

CAS No. :136663-23-5
Formula : C10H9NO3
M.W : 191.18
SMILES Code : COC(=O)C1=CC2=C(C=C1)N=C(C)O2
MDL No. :MFCD00113064
InChI Key :CIGMBXJEQUHKPR-UHFFFAOYSA-N
Pubchem ID :12157467

Safety of [ 136663-23-5 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Application In Synthesis of [ 136663-23-5 ]

* 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.

  • Upstream synthesis route of [ 136663-23-5 ]
  • Downstream synthetic route of [ 136663-23-5 ]

[ 136663-23-5 ] Synthesis Path-Upstream   1~1

  • 1
  • [ 136663-23-5 ]
  • [ 13452-14-7 ]
YieldReaction ConditionsOperation in experiment
97%
Stage #1: With sodium hydroxide In ethanol; water at 20℃; for 2 h;
Stage #2: With hydrogenchloride In ethanol; water
Preparation Example K-2.
2-Methyl-benzoxazole-6-carboxylic acid
To a solution of 2-methyl-benzoxazole-6-carboxylic acid methyl ester (301 mg, 1.57mmol) in ethanol (10mL) was added an aqueous solution of 2N sodium hydroxide (10mL), and the mixture was stirred for 2 hours at room temperature. 2N Hydrochloric acid was added to the reaction mixture to adjust the pH to 4, and the solution was extracted with ethyl acetate.
The organic layer was washed with brine, dried over anhydrous sodium sulfate, then, evaporated in vacuo, and the title compound (270mg, 1.52mmol, 97percent) was obtained.
This was used in the next reaction without purification.
1H-NMR Spectrum (DMSO-d6) δ (ppm): 2.64 (3H, s), 7.73 (1H, d, J=8.0Hz), 7.93(1 H, dd, J=1.2, 8.0Hz), 8.15 (1 H, d, J= 1.2Hz).
97%
Stage #1: at 20℃; for 2 h;
Stage #2: With hydrogenchloride In water
To a solution of 2-methyl-benzoxazole-6-carboxylic acid methyl ester (301 mg, 1.57mmol) in ethanol (10mL) was added an aqueous solution of 2N sodium hydroxide (10mL), and the mixture was stirred for 2 hours at room temperature. 2N Hydrochloric acid was added to the reaction mixture to adjust the pH to 4, and the solution was extracted with ethyl acetate. The organic layer was washed with brine, dried over anhydrous sodium sulfate, then, evaporated in vacuo, and the title compound (270mg, 1.52mmol, 97percent) was obtained. This was used in the next reaction without purification. 1H-NMR Spectrum (DMSO-d6) δ(ppm) : 2.64 (3H, s), 7.73 (1 H, d, J=8.0Hz), 7.93(1 H, dd, J=1.2, 8.0Hz), 8.15 (1 H, d, J= 1.2Hz).
90% With lithium hydroxide monohydrate; water In tetrahydrofuran for 2 h; To methyl 2-methyl-1,3-benzoxazole-6-carboxylate (8) (12.2 g, 0.064 mol) in THF (300 mL)/H2O (100 mL) was added lithium hydroxide monohydrate (5.4 g, 0.128 mol), and the mixture was vigorously stirred. After 2 h the THF was removed under vacuum. The remaining aqueous phase was acidified with HOAc and exhaustively extracted with CH2Cl2. The pooled organic extract was dried (Na2SO4) and concentrated to give a beige solid (10.2 g, 90percent yield): mp 245–246 °C (lit.40 245–246 °C); TLC (SiO2, ethyl acetate/methanol (90:10), UV) single spot Rf 0.38. 1H NMR (300 MHz, DMSO); δ 2.66 (s, 3H, NCH3), 7.75 (d, J = 8.3 Hz, 1H, H-5), 7.96 (dd, J = 8.3, 1.4 Hz, 1H, H-4), 8.16 (d, J = 0.7 Hz, 1H, H-7), 13.12 (bs, 1H, OH).
65%
Stage #1: With lithium hydroxide monohydrate; water In tetrahydrofuran; methanol at 25℃; for 2 h;
Stage #2: With hydrogenchloride In tetrahydrofuran; methanol
To a solution of methyl 2-methylbenzo[d]oxazole-6-carboxylate (2.0 g, 10 mmol) in tetrahydrofuran/methanol/water (1: 1 : 1, 15 mL) was added lithium hydroxide hydrate (0.88 g, 21 mmol). The resulting mixture was stirred at 25 °C for 2 hours. On completion, the mixture was acidified with hydrochloric acid, resulting in formation of a solid. The solid was collected by filtration, washed with water and dried in vacuo to give compound B-130 (1.2 g, 65percent yield) as a white solid.

References: [1] Patent: EP1782811, 2007, A1, . Location in patent: Page/Page column 60.
[2] Patent: EP1669348, 2006, A1, . Location in patent: Page/Page column 68.
[3] Bioorganic and Medicinal Chemistry Letters, 2012, vol. 22, # 21, p. 6661 - 6664.
[4] Patent: WO2016/100184, 2016, A1, . Location in patent: Paragraph 00323-00324.
[5] Patent: US2007/160538, 2007, A1, . Location in patent: Page/Page column 19-20.
[6] Patent: EP1229027, 2002, A1, . Location in patent: Page 15.
[7] Patent: EP1229028, 2002, A1, . Location in patent: Page 15.
[8] Patent: EP1229037, 2002, A1, . Location in patent: Page 15.
[9] Bioorganic and Medicinal Chemistry Letters, 2011, vol. 21, # 10, p. 2980 - 2985.
 

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