1-[(2-Bromophenyl)thio]-2,4-dimethylbenzene

2-(2, 4-dimethylphenyl sulfinyl) bromobenzene (compound IVA) A mixture of lodo bromo benzene (10 g, 0.0353 moles), 2, 4-dimethyl thiophenol (4.87 g, 0.0353 moles) were stirred in toluene (70 ml) under nitrogen. Cul (0.2g, 0.00105 moles) and neocuproine (0.2g, 0.000958 moles) and sodium t-butoxide (6.8 g, 0.0706 moles) were added. The reaction mixture was heated to 1 10°C for 5-6 hours and then cooled to ambient temperature (r.t.). The reaction mixture was filtered and the clear organic layer was washed with water (2 X 50 ml). The organic layer was dried and the solvent was removed at reduced pressure to afford the title compound. Yield: 98-100percentTo 2L single-mouth bottle, 127.5 g (0.45 mol) of o-bromobenzene iodide was added in that order, 2, 4-dimethylthiophenol, 50.4 g (0.5 mol)Iodide ketone 4.3 g (22.5 mmol)Ethylene glycol (56.0 g, 0.9 mol), Isopropyl alcohol 1.1 L, Potassium trichloride 191.0 g (0.9 mol), Under normal pressure at room temperature stirring into the nitrogen, Vacuum replacement three times, 80-90 ° C reaction 7-8h, Stop heating, After the reaction solution was cooled to room temperature, the mother liquor was spin-dried to obtain an oil at 60-70 ° C, To the oil was added 1.5 L of dichloromethane, Add water 1L, Stirred at room temperature for 10-20 min, Diatomaceous earth filtration, The mother liquor is separated, 15percent sodium chloride washed 1L × 2 times, Washed 1L × 1 times, Anhydrous magnesium sulfate drying more than 4h, The DCM was dried to give 132.2 g (yield: 100percent) of a pale yellow oil.Example 18; Example 17; C20 g 2-bromoiodobenzene (71 mmol) and 9.8 g 2, 4-dimethylthiophenol (71 mmol) were dissolved in 100 ml toluene. The solution was purged with nitrogen before 324 mg PdA mixture of 1.7 g of compound A, 2.8 g of compound B, 0.4 g of cuprous iodide and 2.8 g of 100 to 200 mesh potassium carbonate was weighed into a 100 mL three-necked flask, and 50 mL of DMF was added to the flask. After stirring, 0.6 g of 2-acetylcyclohexanone was added After heating, the mixture was heated to 80 ° C and reacted for 2 hours. The reaction was monitored by TLC. After the completion of the reaction, 100 mL of ethyl acetate and 150 mL of water were added. The filtrate was separated by suction filtration, and the organic phase was washed twice with 100 mL of 0.1N sodium hydroxide solution. The organic phase was dried over anhydrous sodium sulphate for 2 h and concentrated at 45 ° C to give an oil. After 40 mL of petroleum ether was added to the oil, the mixture was stirred for 3 h, filtered and the filter cake was washed twice with a little solvent. And dried in vacuo for 12 h to give 2.1 g of the product as a pale yellow solid. The yield was 72.4percent.In a 100 ml reaction flask, Compound 5 (5.7g, 25mmol) was dissolved in 60ml hydrobromic acid (40percent), 0 slowly sodium nitrite (2.6g, 37.5mmol) in water (30ml), After the reaction was completed at 0 ° C for 1 hour, Completion of the reaction, at 0 , The above solution was slowly added to cuprous bromide (14.3 g, 100 mmol)In 50 ml of hydrobromic acid, The temperature was gradually raised to 70 ° C, the reaction was carried out for 3 hours, The pH was adjusted to 7-8 with 40percent KOH, The reaction mixture was concentrated and extracted with ethyl acetate (100 ml)The organic phases were combined, Dried over anhydrous magnesium sulfate, And concentrated to give 5.7 g of compound (6) in a yield of 78.0percent100 g of S-(2, 4-dimethylphenyl) ethanethioate was suspended in 500 ml of degassed toluene. Then added Pd(dba)2 (3.25 gm, 0.006 mole), rac-BINAP(6.4 gm, 0.01 mole), and sodium tert-butoxide (62.5 g, 0.65 mole) under nitrogen purging. Reaction mixture was heated to 45- 55 °C and then added 2-iodo-1-bromo benzene (165 gm, 0.583 mole). Reaction mixture was stined at 90 - 100 °C for 3 hrs under nitrogen atmosphere. After completion of the reaction, it was cooled to room temperature and added 400 ml of water, and allowed to stir for 15-20 mins. Reaction mixture was allowed to settled and organic layer was separated and concentrated under reduced pressure to give thick viscous oil to give desired product (2- bromophenyl)(2, 4-dimethylphenyl) sulfane (162 gm, 100percent)Intermediate 1 (formula IV) (29.2 g, 100 mmol), N-phenoxycarbonylpiperazine (formula V) (26.8 g, 130 mmol)And tert-butanol (formula VI) (12 ml) was dissolved in 600 ml of toluene, and stirred under nitrogen atmosphere for 10 minutes at room temperature (25 C). To the mixture was added tris(dibenzylideneacetone)dipalladium (0.69 g, 0.75 mmol), Racemic 2, 2-bis(diphenylphosphino)-1, 1-biphenyl (1.40 g, 2.25 mmol), Sodium tert-butoxide (57.7 g, 0.6 mol), Re-nitrogen replacement.Heated at 110 C under nitrogen for 8 h.After the reaction was completed, it was cooled to room temperature and filtered through celite.The filtrate was washed with saturated brine and toluene was removed under reduced pressure.Intermediate 2 (mixture of formula VII and formula I)35.0g.Add intermediate 2 (35.0 g) to 350 ml of methanol, 180 ml of 6N hydrochloric acid, heated to reflux for 2 h.The methanol was removed under reduced pressure, and 500 ml of purified water was added.500ml toluene, The pH was adjusted to 13-14 with 1N sodium hydroxide.The aqueous layer is extracted once with toluene.The combined toluene layer was washed with saturated brine.dry. Remove toluene under reduced pressure, The crude fluoxetine (formula I) was 27.1 g.Intermediate 1 (formula IV) (29.2 g, 100 mmol), N-phenoxycarbonylpiperazine (formula V) (26.8 g, 130 mmol)And tert-butanol (formula VI) (12 ml) was dissolved in 600 ml of toluene, and stirred under nitrogen atmosphere for 10 minutes at room temperature (25 C). To the mixture was added tris(dibenzylideneacetone)dipalladium (0.69 g, 0.75 mmol), Racemic 2, 2-bis(diphenylphosphino)-1, 1-biphenyl (1.40 g, 2.25 mmol), Sodium tert-butoxide (57.7 g, 0.6 mol), Re-nitrogen replacement.Heated at 110 C under nitrogen for 8 h.After the reaction was completed, it was cooled to room temperature and filtered through celite.The filtrate was washed with saturated brine and toluene was removed under reduced pressure.Intermediate 2 (mixture of formula VII and formula I)35.0g.

Molecular Weight:293.22
XLogP3:5.4
Hydrogen Bond Acceptor Count:1
Rotatable Bond Count:2
Exact Mass:291.99213
Monoisotopic Mass:291.99213
Topological Polar Surface Area:25.3
Heavy Atom Count:16
Complexity:219
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes