Tetrahydro-2H-pyran-4-ol

Colorless transparent liquid

To a solution of 8a (5.Og, 50mmol) in THF (25mL) cooled to OInto a 250-mL 3-necked round bottom flask, was placed a solution of tetrahydropyran-4-one (5 g, 50.00 mmol, 1.00 equiv) in tetrahydrofuran (25 mL). Step 1: To a solution of 75 g (0.75 mol) of Compound 22 in THF (150 mL) is added a suspension of 28.4 g (0.75 mol) LiAlHSynthesis of 2-Methyl-2-(tetrahydro-pyran-4-sulfonyl)-propionic acid Step 1: Synthesis of Tetrahydro-pyran-4-ol To a solution of 75 g (0.75 mol) of Tetrahydro-pyran-4-one in THF (150 mL) is added a suspension of 28.4 g (0.75 mol) LiAlHStep 1: Synthesis of Compound A2To a solution of 75 g (0.75 mol) of compound Al in THF (150 mL) is added a suspension of 28.4 g (0.75 mol) L1AIHStep 1: Synthesis of compound D-2To a solution of 75 g (0.75 mol) of compound D-1 in THF (150 mL) is added a suspension of 28.4 g (0.75 mol) L1AIHTo 75 g (0.75 mol) of tetrahydropyran-4-one in THF (150 mL) is added a suspension of 28.4 g (0.75 mol) LiAlHTo 75 g (0.75 mol) of tetrahydropyran-4-one in THF (150 mL) is added a suspension of 28.4 g (0.75 mol) LiAIHTetrahydropyran-4-one (7.5 g, 75 mmol, 1 equiv.) in MeOH (75 mL) was cooled to 0° C. NaBHThe same reaction as in was carried out except for changing methanol to isopropylalcohol in As a result, 32.1 g of tetrahydropyran-4-ol was found to be formed (Reaction yield based on 3-buten-1-ol: 84percent).In a glass flask having an inner volume of 2 liters and equipped with a stirring device, a thermometer, a dropping funnel and a Dean-Stark device was charged 600 ml of 98percent by weight formic acid, and the mixture was heated to 80°C. Thereafter, a solution containing 300 g (4.16 mol) of 3-buten-1-ol and 149.9 g (1.66 mol) trioxane dissolved in 600 ml of 98percent by weight formic acid was gradually added dropwise to the above mixture over 4.5 hours, and under nitrogen atmosphere, the mixture was subjected to cyclization reaction at the same temperature for 8 hours. Then, after cooling the reaction mixture to room temperature, 5.4 g (56 mmol) of methanesulfonic acids and 600 ml of ethanol were added to the mixture, and the resulting mixture was heated up to 64°C under normal pressure, whereby solvolysis was carried out while removing by-producing ethyl formate. Moreover, after this operation was repeated three times, the reaction mixture was distilled under reduced pressure (85 to 87°C, 173Pa) to obtain 347 g of tetrahydropyran-4-ol (Isolation yield based on 3-buten-1-ol: 81.6percent) as a colorless liquid with a purity of 99.2percent (areal percentage according to gas chromatography). Example 3 (Synthesis of tetrahydropyran-4-ol) The same reaction as in was carried out except for changing methanol to ethanol in As a result, 30.9 g of tetrahydropyran-4-ol was found to be formed (Reaction yield based on 3-buten-1-ol: 81percent). Example 5 (Synthesis of tetrahydropyran-4-ol) In a glass flask having an inner volume of 500 ml and equipped with a stirring device, a thermometer, a dropping funnel and a Dean-Stark device were charged 10.0 g (139 mmol) of 3-buten-1-ol, 5.0 g (56 mmol) of trioxane and 40 ml of 98percent by weight formic acid, the mixture was subjected to cyclization reaction under nitrogen atmosphere at 80°C for 4 hours. Then, 0.2 g (2 mmol) of methanesulfonic acid and 50 ml of ethanol were added to the mixture and the resulting mixture was heated up to 64°C, whereby solvolysis was carried out while removing by-producing ethyl formate. Moreover, after the operation was repeated, when the reaction mixture was analyzed by gas chromatography (internal standard method), 13.1 g of tetrahydropyran-4-ol was found to be formed (Reaction yield based on 3-buten-1-ol: 92percent).In a glass flask having an inner volume of 500 ml and equipped with a stirring device, a thermometer, a dropping funnel and a Dean-Stark device were charged 27.0 g (374 mmol) of 3-buten-1-ol, 13.5 g (150 mmol) of trioxane and 133 ml of 98percent by weight formic acid, and the mixture was subjected to cyclization under nitrogen atmosphere at 80°C for 4 hours. Then, formic acid was distilled off from the reaction mixture under reduced pressure, 1 g (10 mmol) of methanesulfonic acid and 200 ml of methanol were added to the residue, and the resulting mixture was heated up to 64°C under normal pressure, whereby solvolysis was carried out while removing by-producing methyl formate. Moreover, after this operation was repeated, when the reaction mixture was analyzed by gas chromatography (internal standard method), 30.2 g of tetrahydropyran-4-ol was found to be formed (Reaction yield based on 3-buten-1-ol: 79percent).

Tetrahydro-4-pyranol is a building block of various organic compounds and pharmaceuticals.

Molecular Weight:102.13
XLogP3:-0.1
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:2
Exact Mass:102.068079557
Monoisotopic Mass:102.068079557
Topological Polar Surface Area:29.5
Heavy Atom Count:7
Complexity:48
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes