ChemicalBook CAS DataBase List Tetrahydropyranyl-4-acetic acid

Tetrahydropyranyl-4-acetic acid synthesis

12synthesis methods

Product Name:Tetrahydropyranyl-4-acetic acid
CAS Number:85064-61-5
Molecular formula:C7H12O3
Molecular Weight:144.17

103260-44-2

85064-61-5

General procedure for the synthesis of tetrahydropyran-4-acetic acid from ethyl tetrahydropyran-4-yl-acetate: 1. a solution of sodium hydroxide (15.9 g, 44.06 mmol) in water (150 ml) was added dropwise to a methanolic solution of ethyl 2-(tetrahydro-2H-pyran-4-yl)acetate (15 g, 8.81 mmol) at 0 °C or lower. 2. The mixture was stirred at room temperature for 15 hours. 3. The solvent was removed from the reaction mixture by depressurized distillation. 4. The aqueous layer was adjusted to pH 3 by adding 1 M hydrochloric acid and extracted with ethyl acetate. 5. Wash the organic layer with saturated brine and dry with anhydrous sodium sulfate. 6. The filtrate was concentrated under pressure to give tetrahydropyran-4-acetic acid as a colorless solid (12.0 g, 94%). This compound can be used in the next step without further purification. 7. Benzyl bromide (14.3 g, 83.33 mmol) was added dropwise to a suspension of tetrahydropyran-4-acetic acid (10.0 g, 69.44 mmol) and anhydrous potassium carbonate (28.8 g, 208.3 mmol) in acetonitrile (100 ml) at room temperature. 8. The mixture was refluxed for 48 hours. 9. The solvent was removed from the mixture by decompression distillation and the residue was diluted with water and extracted with dichloromethane. 10. The organic layer was dried over anhydrous sodium sulfate. 11. The filtrate was concentrated under pressure and the residue was chromatographed on a silica gel column (hexane: ethyl acetate = 9:1) to afford benzyl tetrahydropyran-4-acetate as an oil (12.0 g, 75% yield). 12. 12. Product characterization data: 1H-NMR (400 MHz, CDCl3): δ (ppm) 7.39-7.34 (m, 5H), 5.12 (s, 2H), 3.95-3.92 (m, 2H), 3.42-3.36 (m, 2H), 2.30 (d, J = 7.2 Hz, 2H), 2.09-1.99 (m, 1H) 1.64-1.61 (m, 2H), 1.39-1.29 (m, 2H); MS (ESI): m/z 234 (M+).

103260-44-2
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$10.00/100mg

85064-61-5
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$6.00/100mg

Yield: 94%

Reaction Conditions:

with water;sodium hydroxide in methanol at 0 - 20; for 15 h;

Steps:

3.3 Step 3: Benzyl 2-(tetrahydro-2H-pyran-4-yl)acetate
A solution of sodium hydroxide (15.9 g, 44.06 mmol) in water (150 ml) was added dropwise to a solution of ethyl 2-(tetrahydro-2H-pyran-4-yl)acetate (15 g, 8.81 mmol) in methanol (150 ml) at a temperature of 0 °C or below, and the mixture was stirred at room temperature for 15 hr. The solvent of the reaction mixture was removed by distillation under reduced pressure, and the water layer was adjusted to pH 3 by the addition of 1 M hydrochloric acid and was extracted with ethyl acetate. The organic layer was washed with saturated brine and was dried over anhydrous sodium sulfate, and the filtrate was concentrated under reduced pressure to give a corresponding acid as a colorless solid (12.0 g, 94%). This compound was used in the next step without further purification. Benzyl bromide (14.3 g, 83.33 mmol) was added dropwise to a suspension of this compound (10.0 g, 69.44 mmol) and anhydrous potassium carbonate (28.8 g, 208.3 mmol) in acetonitrile (100 ml) at room temperature, and the mixture was refluxed for 48 hr. The solvent of the mixture was removed by distillation under reduced pressure, the residue was diluted with water and was extracted with dichloromethane, and the organic layer was dried over anhydrous sodium sulfate. The filtrate was concentrated under reduced pressure, and the residue was chromatographed on silica gel column (hexane:ethyl acetate = 9:1) to give the tile compound as an oil (12.0 g, yield 75%). 1H-NMR (400 MHz, CDCl₃): δ (ppm) 7.39-7.34 (m, 5H), 5.12 (s, 2H), 3.95-3.92 (m, 2H), 3.42-3.36 (m, 2H), 2.30 (d, J = 7.2 Hz, 2H), 2.09-1.99 (m, 1H) 1.64-1.61 (m, 2H), 1.39-1.29 (m, 2H); MS (ESI): m/z 234 (M⁺).

References:

Meiji Seika Pharma Co., Ltd.;MORINAKA, Akihiro;MAEBASHI, Kazunori;IDA, Takashi;HIKIDA, Muneo;YAMADA, Mototsugu;ABE, Takao EP2737900, 2014, A1 Location in patent:Paragraph 0114; 0117-0118