(S)-1-(3-Ethoxy-4- Methoxyphenyl)-2-(Methylsulfony

In a 50 mL hydrogenation tube, the obtained 1.35 g of a white solid was dissolved in 20 mL of methanol, and 270 mgOf 10percent Pd / C, charged with 0.1 MPa of hydrogen, stirred at 25 ° C for 24 h. Filtration, steaming to remove the solvent, the crude over-alkaline trioxide(S) -2- [1- (3-ethoxy-4-methoxyphenyl)] - 1-methanesulfonyl-2-ethylamine as a white solid, The reaction yield was 89.2percent and the enantiomeric excess was 94.9percent.Example 3[011 8j After a mixture of (1 S)- 1 -(3 -ethoxy-4-methoxyphenyl)-2-methanesulfonyl- ethylamine N-acetyl-L-Leucine salt (1.10 kg, 2.46 moles), deionized water (4.40 L), and dichloromethane (DCM, 5.50 L) was charged into a reaction vessel, a solution of sodium hydroxide (196.0 g, 4.90 moles) in 1.00 L of deionized water was charged into the reaction vessel over about 5 minutes at 15-25°C. The resulting mixture was stirred for at least 10 minutes at 15-25°C and then the aqueous and organic phases were allowed to separate. The pH of the upper aqueous phase was maintained or adjusted at pH 13-14. The phases were separated and the upper aqueous phase was extracted with DCM (2x4.4 L). The pH of the aqueous phase was maintained at 13-14 throughout the extractions. The DCM extracts were combined and washed with deionized water (3.3 L) until the pH of the aqueous phase reached 11 or less. DCM was removed under vacuum below 35°C. The water content of the residual solid should be <0.1percent w/w as measured by Karl Fisher titration. The residual solid was dried azeotropically with more DCM. The solid was dried to a constant weight in vacuo at 30-35°C to give (1S)-1-(3-ethoxy-4- methoxyphenyl)-2-methanesulfonyl-ethylamine as a white powder (639.0-672.0 g, 95-100percent yield).6.5.3. Preaparation of (S)-1-(4-methoxy-3-ethoxyphenyl)-2-methanesulfonylethylamine (II) 6.5.3.General procedure: For each reaction, a mixture of bis(1, 5-cyclooctadiene)rhodium(I) trifluoromethanesulfonate (9 mg, 0.018 mmol), 2, 2, 2-trifluoroethanol (3 mL), and the appropriate ligand (0.037 mmol) or a preformed complex of the ligand and metal (0.018 mmol) was prepared under nitrogen. Then, 1-(3-ethoxy-4-methoxyphenyl)-2-(methylsulfonyl)ethenamine (100 mg, 0.37 mmol) was added. The resultant mixture was heated to 50° C. and hydrogenated under 250 psig hydrogen pressure. After 18 h, the mixture was removed from the hydrogenator and monitored by achiral HPLC (Hypersil BDS CA mixture of 1-(3-ethoxy-4-methoxyphenyl)-2-(methylsulfonyl)ethanone (2 g, 7.34 mmol) and ammonium acetate (1.868 g, 24.24 mmol) in TFE (20 mL) was heated to reflux. The batch was slowly distilled, while a solution of NHFinally, the N-benzylated aminosulfone derivative Compound D (100 g, 0.211 mol) was hydrogenated with 5percent Pd/C (5.0 g), in methanol solvent (1000 ml) and at room temperature, to afford the pure S-aminosulfone Compound B (49-54 g) with 86-94percent yield and >99percent chiral and chemical purity.To the product from Step 1 (0.30 g, 0.81 mmol) was added 6N HCl (15 mL), and the resulting mixture was heated to 85° C. for 16 h, and then cooled to 20° C. The mixture was filtered, and the filtrate was evaporated. The residue was partitioned between 10percent KGeneral procedure: For each reaction, a mixture of bis(1, 5-cyclooctadiene)rhodium(I) trifluoromethanesulfonate (9 mg, 0.018 mmol), 2, 2, 2-trifluoroethanol (3 mL), and the appropriate ligand (0.037 mmol) or a preformed complex of the ligand and metal (0.018 mmol) was prepared under nitrogen. Then, 1-(3-ethoxy-4-methoxyphenyl)-2-(methylsulfonyl)ethenamine (100 mg, 0.37 mmol) was added. The resultant mixture was heated to 50° C. and hydrogenated under 250 psig hydrogen pressure. After 18 h, the mixture was removed from the hydrogenator and monitored by achiral HPLC (Hypersil BDS CGeneral procedure: For each reaction, a mixture of bis(1, 5-cyclooctadiene)rhodium(I) trifluoromethanesulfonate (9 mg, 0.018 mmol), 2, 2, 2-trifluoroethanol (3 mL), and the appropriate ligand (0.037 mmol) or a preformed complex of the ligand and metal (0.018 mmol) was prepared under nitrogen. Then, 1-(3-ethoxy-4-methoxyphenyl)-2-(methylsulfonyl)ethenamine (100 mg, 0.37 mmol) was added. The resultant mixture was heated to 50° C. and hydrogenated under 250 psig hydrogen pressure. After 18 h, the mixture was removed from the hydrogenator and monitored by achiral HPLC (Hypersil BDS CTo a 2 L round bottom flask equipped with a mechanical stirrer, thermometer, and condenser, charge 500 mL of THF followed by (£/Z)- l-(3-ethoxy-4-methoxyphenyl)-2-(methylsulfonyl) ethenamine (50 grams, 0.184 mole) at 25-30 °C. The mixture was cooled at -10 °C to 0 °C. Charge sodium borohydride (8.36 grams, 0.221 mole) and L-valinol (4.7 grams, 0.046 mole) to reaction mass and stir for 1 hour at -10 °C to 0 °C. To the cooled the reaction mass add mixture of Borontrifluoride diethyl etherate (28.56 mL, 0.221 moles) in THF (30 mL) in 1 hour at - 10 to 0 °C. The mixture was allowed to warm at 25-30 °C in 2-3 hours and stirred overnight at 25-30 °C. Water (250 mL) was charged to reaction mass at 0-10 °C. After warming to 25-30 °C, the THF was distilled out from reaction mixture under vacuum. Charge ethyl acetate (200 mL) to reaction mass and add concentrated Hydrochloric acid (50 mL) till pH 2-3. Separate the organic and aqueous layer. To the aqueous layer charge 30 percent sodium hydroxide (225 mL) till pH 10-1 1. Extract the compound by using dichloromethane (2 *250 mL). Club the organic layers and wash with 10 percent aqueous sodium chloride solution. Distilled off dichloromethane for organic layer. To the crude solid charge THF (25 mL) and stir for 30 minutes. Filter the isolated solid on Buchner funnel. The wet solid dried in hot air oven at 40-45 °C for 4 hours to provide l-(3-ethoxy-4-methoxyphenyl)-2-(methylsulfonyl)ethanamine as off white solid (41.7 grams, 83 percent yield). NMR (DMSO-d

Molecular Weight:273.35
XLogP3:0.5
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:5
Rotatable Bond Count:6
Exact Mass:273.10347926
Monoisotopic Mass:273.10347926
Topological Polar Surface Area:87
Heavy Atom Count:18
Complexity:339
Defined Atom Stereocenter Count:1
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes