Biphenyl-4-Ethanol

Method 2: Sodium borohydride (1.2 g, 31.7 mmol) was added to a flask containing tetrahydrofuran (THF) (40 mL) stirred under nitrogen. 4-Biphenylacetic acid (5.0 g, 23.6 mmol) was then added slowly over 20 min while the stirred reaction mixture was maintained at 20-30 Example 2.62: Preparation of l-{4'-[2-((λ)-2-Methyl-pyrrolidin-l-yl)-ethyI]-biphenyl-4- suIfonyl}-piperidine-4-carboxylic Acid Ethyl Ester (Compound 90); Step A: Preparation of Intermediate 2-Biphenyl-4-yl-ethanoI; To a 1000 mL round-bottomed flask containing 4-biphenylacetic acid (20.0 g, 94.2 mmol) in THF (250 mL) at 0 Step A: Preparation of Intermediate 2-Biphenyl-4-yl-ethanol.To a 1000 mL round-bottomed flask containing 4-biphenylacetic acid (20.0 g, 94.2 mmol) in THF (250 mL) at 0 Under nitrogen atmosphere, to a cooled (0 °C) suspension of LiA1H4 (2.0 M in THF solution, 5.65 mL, 11.3 mmol) in dry Et20 (20 mL), commercially available 4-biphenyl-acetic acid (0.6 g, 2.83 mmol) in dry Et20 (8.0 mL) was added dropwise. The resulting reaction mixture was stirred at r.t. for 4 h, and then cooled to 0 °C. H20 (0.50 mL) was slowly added, followed by 3.0 M KOH solution (0.50 mL) and additional H20 (1.5 mL). The mixture wasstirred at 0 °C for 1 h and then filtered off. The organic layer was dried over Na2504, filtered and concentrated to dryness, affording the title compound (0.53 g, 87percent), which was used in the next step without any further purification. ‘H NMR (DMSO-d6) ö 7.67—7.61 (m, 2H), 7.59—7.54 (m, 2H), 7.50—7.42 (m, 2H), 7.3 8—7.28 (m, 3H), 4.64 (t, 1H, J= 5.2 Hz), 3.78—3.53 (m, 2H), 2.76 (t, 2H, J= 7.0 Hz).Step A: Preparation of 2-Biphenyl-4-yl-ethanol.To dilute the hydrogen gas byproduct continuously vented from the reactor, a vigorous flow of nitrogen through the reactor is maintained throughout the entire preparation until the quench with aqueous sodium hydroxide is completed. To a 50 L reactor containing isopropyl acetate (16.7 L) is added sodium borohydride (0.762 Kg, 20.14 mole, 1.60 eq). The sodium borohydride is rinsed into the reactor with additional isopropyl acetate (1 L). 4-Biphenylacetic acid (2.67 Kg, 12.58 moles, 1.00 eq) is then added sufficiently slowly to maintain the stirred reactor contents at 0°-8°C with reactor jacket cooling. The biphenylacetic acid is rinsed into the reactor with additional isopropyl acetate (1 L). The reactor contents are then warmed to 25°C for one hour and then cooled again to -5°-0°C. Borontrifluoride diethyletherate (3.584 Kg, 25.25 moles, 2.01 eq) is then added at a constant rate over a three hour period while the stirred reactor contents are maintained at 0°-5°C with reactor jacket cooling. The reactor contents are warmed to 20°-25°C, and stirring at that temperature is continued until substantially complete 4-biphenylacetic acid conversion is verified by liquid chromatography. (Substantially complete conversion is typically achieved in 1-12 hours.) A solution of sodium hydroxide (3.355 Kg, 83.9 moles, 6.67 eq) in water (15.0 L) is then added sufficiently slowly to maintain the stirred reactor contents at 10°-20°C with reactor jacket cooling. The reactor contents are heated to 40Dissolve LiAlH4 (1.1 eq) in anhydrous THF.Under ice bath conditions, Slowly add the compound of formula 1-1 (Biphenyl-4-carboxylic acid, 1.0 eq) in THF, After the addition was completed, the reaction solution was heated to a stirring reaction for 12 hours.The reaction was terminated and the reaction was quenched by the addition of 15percent NaOH solution.The resulting mixture was extracted with ethyl acetate.Filtered, concentrated and column chromatographyGet white flaky crystals, That is, the compound of the formula 1-2, the yield is 70percent.

Molecular Weight:198.26
XLogP3:3
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:1
Rotatable Bond Count:3
Exact Mass:198.104465066
Monoisotopic Mass:198.104465066
Topological Polar Surface Area:20.2
Heavy Atom Count:15
Complexity:164
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes