(Tetrahydro-2H-pyran-4-yl)methanol

Colorless liquid

Preparation 5: (Tetrahydropyran-4-yl)methanoI; OHTo a suspension of LiAltL, (56g, 1.47mol) in diethyl ether (2L) under argon was added methyl tetrahydro-2H-pyran-4-carboxylate (270g, 1.88mol) in diethyl ether (ca. 200mL) under reflux over a period of 1.75h. After addition was complete reflux was continued for a further lh. TLC (diethyl ether) indicated a small amount of ester remained, so further LiAltLt (lOg, 0.26mol) was added and reflux continued for lh. Water (66mL) was added, then 15percent NaOH solution (66mL), followed by further water (198mL). The solid was filtered and dried to give the crude product, which was redissolved in DCM (800 ml), dried (MgS0Preparation 3:Preparation 3: (Tetrahydropyran-4-yl)methanoI; To a suspension of LiAlFL, (56g, 1.47mol) in diethyl ether (2L) under argon was added methyl tetrahydro-2H-pyran-4-carboxylate (270g, 1.88mol) in diethyl ether (ca. 200mL) under reflux over a period of 1.75h. After addition was complete reflux was continued for a further lh. TLC (diethyl ether) indicated a small amount of ester remained, so further LiAlFL, (lOg, 0.26mol) was added and reflux continued for lh. Water (66mL) was added, then 15percent NaOH solution (66mL), followed by further water (198mL). The solid was filtered and dried to give the crude product, which was redissolved in DCM (800 ml), dried (MgS04), filtered and the solvent removed to afford the title compound (207 g, 94percent yield). NMR was consistent with the above structure.Step 1: To a solution of 250 mL of LiAlHSynthesis of 2-Methyl-2-(tetrahydro-pyran-4-ylmethanesulfonyl)-propionic acid Step 1: Synthesis of (Tetrahydro-pyran-4-yl)-methanol To a solution of 250 mL of LiAlHAcid Method B:Synthesis of Compound B6Step 1: Synthesis of Compound B2To a solution of 250 mL of LiAlHStep 1: Synthesis of compound B-2 To a solution of 250 mL of LiAlHTo 250 mL of LiAlHTo 250 mL of LiAIHTo a solution of methyl tetrahydro-2H-pyran-4-carboxylate (3 g, 21 mmol) in tetrahydrofuran (30 mL) undernitrogen atmosphere was slowly added lithium aluminum hydride (1.18g, 31 mmol) in batches at 0°C. The reaction wasstirred at 0°C for 1 hour, then carefully quenched with H2O (1.2 mL), NaOH (1.2 mL, 15percent), H2O (3.6 mL) successivelyand stirred for 20 minutes. The mixture was filtered and the filtrate was concentrated to give the title compound (2.1 g, 87percent yield) as a colorless liquid. 1H NMR (400 MHz, CHLOROFORM-d) ppm 4.00 (dd, J=4.02, 11.04 Hz, 1H), 3.51 (t, J=5.77 Hz, 1H), 3.41 (dt, J=1.76, 11.67 Hz, 1H), 1.70-1.81 (m, 1H), 1.66 (d, J=13.05 Hz, 2H), 1.27-1.40 (m, 3H).Methyl tetrahydro-2H-pyran-4-carboxylate (5 g, 34.68 mmol, 1.0 equiv) was dissolved in THE (60 mL) and methanol (10 mL). Sodium borohydride (2.62 g, 69.36 mmol, 2.0 equiv) was added in portions and the reaction mixture was stirred at room temperature for 3 hours. The reaction mixture was quenched with saturated aqueous ammonium chloride solution and extracted with EtOAc. The organic layer was washed with brine, dried over sodium sulfate and concentrated to afford the desired product 3.1.22a (3.2 g, 80 percent yield). 1H NMR (400 MHz, DMSO) 6 3.96 — 3.75 (m, 2H), 3.66 — 3.58 (m, 2H), 3.36 (dd, J = 6.9, 4.7 Hz, 2H), 3.33—3.17 (m, 2H), 1.81—1.70 (m, 2H), 1.63—1.48 (m, 2H).EXAMPLE 77A To an ice-cooled solution of 2.60 g (20.0 mmol) of tetrahydropyran-4-carboxylic acid in 8 mL of THF was added 21 mL (21 mmol) of 1.0M borane in THF. General procedure: The hydrogenation of carboxylic acids or other substrates was performed in a high-pressure stainless-steel autoclave (Xinyuan Chemical Machinery, Series CJK, 300 mL) with a maximum stirring rate of 1500 r/min. In a typical experiment, 0.2 g of catalyst (or without catalyst for the control experiment), 3 mmol of the substrate, and 100 mL alkane solvent (n-hexane, n-heptane, i-octane, or n-dodecane) were well mixed in the autoclave and purged with pure nitrogen at room temperature. The gas supply and discharge were carried out manually through needle valves. The autoclave was rapidly heated to the desired temperature and hydrogen was introduced at 2 MPa to initiate the reaction. The reaction pressure was kept at 2 MPa with a small negative deviation (∼0.2 MPa) owing to the consumption of hydrogen. Samples of the liquid phase were continuously taken through a sampling tube with a filter at certain intervals. The stirring rate was kept at 750 r/min during the reaction.Ethyl tetrahydro-2H-pyran-4-carboxylate (5.0 g, 34.7 mmol) was added to a stirred solution of LiAlH4 (4.0 g, 104 mmol) in THF (100 mE) at 0° C. and the reaction mixture was stirred for 1 h. Ethyl acetate (20 mE) was added dropwise to the reaction mixture followed by addition of 10percent aq.NaOH and the resulting mixture was stirred for additional 30 mm. Reaction mass was filtered through Celite and the filtrate was concentrated under reduced pressure to give (tetrahydro-2H-pyran-4-yl)methanol (9) as a colorless oil. Yield (3.9 g, 96percent); ‘H NMR (400 MHz, DMSO-d5) δ 4.46 (bs, 1H), 3.82 (dd, J=i0.8, 8.0 Hz, 2H), 3.25-3.22 (m, 4H), 1.62-1.52 (m, 3H), 1.18-1.04 (m, 1H).

Molecular Weight:116.16
XLogP3:0.1
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:1
Exact Mass:116.083729621
Monoisotopic Mass:116.083729621
Topological Polar Surface Area:29.5
Heavy Atom Count:8
Complexity:57.5
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes