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Chemical Structure| 158984-84-0 Chemical Structure| 158984-84-0

Structure of 158984-84-0

Chemical Structure| 158984-84-0

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Product Details of [ 158984-84-0 ]

CAS No. :158984-84-0
Formula : C15H18F3NO5S
M.W : 381.37
SMILES Code : O=C(N1CC2=C(C=C(OS(=O)(C(F)(F)F)=O)C=C2)CC1)OC(C)(C)C
English Name :tert-Butyl 6-(trifluoromethylsulfonyloxy)-3,4-dihydroisoquinoline-2(1H)-carboxylate
MDL No. :MFCD22124652

Safety of [ 158984-84-0 ]

Application In Synthesis of [ 158984-84-0 ]

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

  • Downstream synthetic route of [ 158984-84-0 ]

[ 158984-84-0 ] Synthesis Path-Downstream   1~10

  • 1
  • [ 358-23-6 ]
  • [ 158984-83-9 ]
  • [ 158984-84-0 ]
YieldReaction ConditionsOperation in experiment
88% With pyridine at 0℃; for 0.166667h;
65% With triethylamine In dichloromethane at 0 - 20℃; for 2.16h;
56% With triethylamine In dichloromethane at 0 - 20℃; 15 tert-butyl 6-[(trifluoromethyl)sulfonyl]oxy}-3,4-dihydroisoquinoline-2(1H)-carboxylate To a dichloromethane solution (5.0 mL) of tert-butyl 6-hydroxy-3,4-dihydroisoquinoline-2(1H)-carboxylate (249mg, 1.00 mmol), trifluoromethanesulfonic anhydride (337 mL, 2.00 mmol) and triethylamine (558 mL, 4.00 mmol) wereadded at 0°C and the resultant reaction solution was stirred overnight at room temperature. After completion of thereaction, a brine was added to the reaction solution and the resultant mixture was extracted with ethyl acetate. Theorganic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The obtained residuewas purified by silica gel column chromatography (hexane/ethyl acetate = 8/1) to obtain the title compound (Rf15) (214mg, yield 56%) as a colorless oily product
56% With triethylamine In dichloromethane at 0 - 20℃; 15 Reference Synthesis Example 15 Tert-butyl 6-[(trifluoromethyl)sulfonyl]oxy}-3,4-dihydroisoquinoline-2(1H)-carboxylate To a dichloromethane solution (5.0 mL) of tert-butyl 6-hydroxy-3,4-dihydroisoquinoline-2(1H)-carboxylate (249 mg, 1.00 mmol), trifluoromethanesulfonic anhydride (337 µL, 2.00 mmol) and triethylamine (558 µL, 4.00 mmol) were added at 0°C and the resultant reaction solution was stirred overnight at room temperature. After completion of the reaction, a brine was added to the reaction solution and the resultant mixture was extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (hexane/ethyl acetate = 8/1) to obtain the title compound (Rf15) (214 mg, yield 56%) as a colorless oily product.
With triethylamine In dichloromethane at 0℃;
With triethylamine In dichloromethane 45.a 5-[6-(4-Chlorophenyl)-3,4-dihydro-1H-isoquinolin-2-ylmethyl]-2-methyl-pyrimidin-4-ylamine a) Firstly 0.22 ml (0.00160 mol) of triethylamine and then 0.26 ml (0.00155 mol) of trifluoromethanesulphonic anhydride were added dropwise under argon to an ice-cold solution of 0.38 g (0.00152 mol) of tert.-butyl 6-hydroxy-3,4-dihydro-1H-isoquinoline-2-carboxylate in 7.5 ml of dichloromethane. The mixture was stirred at room temperature for 1 hour, poured into saturated sodium hydrogen carbonate solution, extracted with ethyl acetate and completely freed from the solvents. 0.66 g of oily crude tert.-butyl 6-(trifluoromethanesulphonyloxy)-3,4-dihydro-1H-isoquinoline-2-carboxylate was obtained.
With triethylamine In dichloromethane 46.a 5-[6-(3,5-Dichlorophenyl)-3,4-dihydro-1H-isoquinolin-2-ylmethyl]-2-methyl-pyrimidin-4-ylamine a) Firstly 1.46 ml (0.0105 mol) of triethylamine and then 1.7 ml (0.0102 mol) of trifluoromethanesulphonic anhydride were added dropwise under argon to an ice-cold solution of 2.49 g (0.010 mol) of tert.-butyl 6-hydroxy-3,4-dihydro-1H-isoquinoline-2-carboxylate in 80 ml of dichloromethane. The mixture was stirred at room temperature for 1 hour, poured into saturated sodium hydrogen carbonate solution, extracted with ethyl acetate and completely freed from the solvents. 3.81 g of oily crude tert.-butyl 6-(trifluoromethanesulphonyloxy)-3,4-dihydro-1H-isoquinoline-2-carboxylate were obtained.
Stage #1: trifluoromethylsulfonic anhydride; N-tert-butoxycarbonyl-6-hydroxy-1,2,3,4-tetrahydroisoquinoline With triethylamine In dichloromethane at 0℃; Stage #2: With dmap In dichloromethane at 0 - 20℃; for 2h; 1.D.3 To a solution of 6-hydroxy-3,4-dihydro-lH-isoquinoline-2-carboxylic acid tert-butyl ester (12.46 g, 50 mmol) in anhydrous DCM (150 ml) cooled to 0 0C is added TEA (10.45 ml, 75 mmol, 1.5 eq.), followed by the addition of trifluoromethanesulfonic anhydride (15.51 g, 55 inmol, 1.1 eq.) dropwise. After the addition is completed, 4-dimethylaminopyridine is added (100 mg). The reaction mixture is stirred at 0 0C for 1 h, then warmed to it, and stirred for an additional 1 h. Water (200 ml) is added to quench the reaction. The DCM layer is collected, washed with water and brine, and dried over sodium sulfate, and the solvent is removed under reduced pressure. Purification of the residue through silica gel flash chromatography (hexane/EA 10:1) gives the title compound.
With triethylamine In dichloromethane at 0 - 20℃; L-1.3 To a solution of 1,1-dimethylethyl 6-hydroxy-3,4-dihydro-2(1H)-isoquinolinecarboxylate (4.92 g; 19.8 mmol, as per step 2 above) and Et3N (3.31 mL; 23.8 mmol) in CH2Cl2 at 0° C. was added Tf2O (3.65 mL; 21.7 mmol), dropwise over 3 minutes. The mixture was slowly warmed to room temperature (overnight), poured into water and the layers were separated. The aqueous layer was extracted with CH2Cl2 (×2), combined organics were washed (water, brine), dried over Na2SO4 and concentrated in vacuo. The residue was purified by flash chromatography (EtOAc/hexanes), affording the title compound as a colorless gum which gradually solidified. 1H NMR (400 MHz, CDCl3) δ 1.49 (s, 9H), 2.87 (t, J=5.7 Hz, 2H), 3.66 (br. t, J=5.5 Hz, 2H), 4.59 (s, 2H), 7.04-7.12 (m, 2H), 7.18 (d, J=8.4 Hz, 1H).
With triethylamine In dichloromethane at 0℃; V-16.3 1,1-dimethylethyl 6-[(trifluoromethyl)sulfonyl]oxy}-3,4-dihydro-2(1H)-isoquinolinecarboxylate To a solution of 1,1-dimethylethyl 6-hydroxy-3,4-dihydro-2(1H)-isoquinolinecarboxylate (0.146 g; 0.586 mmol) and Et3N (0.17 mL; 1.2 mmol) in CH2Cl2(5 mL) at 0° C. was added Tf2O (0.11 mL; 0.67 mmol (dropwise over 2 min. The mixture was stirred overnight, gradually warming to room temperature, diluted with CH2Cl2, washed (water, brine), dried over Na2SO4and concentrated in vacuo. The residue was purified by flash chromatography (EtOAc/hexanes), affording the title compound as a colorless gum which slowly solidified.
With pyridine In dichloromethane at 0℃; for 1h; 128.A Step A. teil-butyl 6-(((trifiuoromethvl)sulfonvi)oxy)-3,4-dihydroisoquinohne- 2(H)-carboxylate. To a solution of pyridine (16.22 ml, 201 mmoi) and tert-butyi6-hydroxy-3,4-dihydroisoquinoline-2(1l-{)-carboxylate (50.0 g, 201 mmol) in DCM (600 ml), Tf2.O (33.9 ml. 201 inmol) was added dropwise at 0°C and the mixture was stirred at 0 °C for I h. The reaction mixture was diluted with DCM (800 niL), washed with water (2 x200 mL) and brine (2 x 2CC mE). The organic solution was dried, filtered, concentrated in vacuo and purified by silica gel chromatography (PE:EtOAc=80: 1 ‘1 0:1) to give the title compound.
Stage #1: trifluoromethylsulfonic anhydride; N-tert-butoxycarbonyl-6-hydroxy-1,2,3,4-tetrahydroisoquinoline With triethylamine In dichloromethane at 0℃; Stage #2: With dmap In dichloromethane at 0 - 20℃; for 2h; 1.IV.3 To a solution of 6-hydroxy-3,4-dihydro-lH-isoquinoline-2-carboxylic acid tert-bxxty ester (12.46 g, 50 mmol) in anhydrous DCM (150 ml) cooled to 0 0C is added TEA (10.45 ml, 75 mmol, 1.5 eq.), followed by trifluoromethanesulfonic anhydride (15.51 g, 55 mmol, 1.1 eq.) added dropwise. After the addition is complete, 4-dimethyIaminopyridine is added (100 mg). The reaction mixture is stirred at 0 0C for 1 hr, then warmed to rt and stirred for an additional 1 hr. Water (200 ml) is added to quench the reaction. The DCM layer is collected, washed with water and brine, and dried over sodium sulfate, and the solvent is removed under reduced pressure. Purification of the residue through silica gel flash chromatography (hexane/EtOAc 10:1) gives the title compound. MS (+VE) m/z 382.2 (M+ +1).
With pyridine at 0 - 20℃; for 2.16667h;

References: [1]Haginoya, Noriyasu; Kobayashi, Syozo; Komoriya, Satoshi; Yoshino, Toshiharu; Suzuki, Makoto; Shimada, Takashi; Watanabe, Kengo; Hirokawa, Yumiko; Furugori, Taketoshi; Nagahara, Takayasu [Journal of Medicinal Chemistry, 2004, vol. 47, # 21, p. 5167 - 5182].
[2]Chekler, Eugene L. Piatnitski; Unwalla, Rayomond; Khan, Taukeer A.; Tangirala, Raghuram S.; Johnson, Mark; St. Andre, Michael; Anderson, James T.; Kenney, Thomas; Chiparri, Sue; McNally, Chris; Kilbourne, Edward; Thompson, Catherine; Nagpal, Sunil; Weber, Gregory; Schelling, Scott; Owens, Jane; Morris, Carl A.; Powell, Dennis; Verhoest, Patrick R.; Gilbert, Adam M. [Journal of Medicinal Chemistry, 2014, vol. 57, # 6, p. 2462 - 2471].
[3]Current Patent Assignee: NISSAN CHEMICAL INDUSTRIES - TW2016/7941, 2016, A Location in patent: Paragraph 0215.
[4]Current Patent Assignee: NISSAN CHEMICAL INDUSTRIES - EP3053917, 2016, A1 Location in patent: Paragraph 0244.
[5]Selnick; Smith; Tebben [Synthetic Communications, 1995, vol. 25, # 20, p. 3255 - 3261].
[6]Current Patent Assignee: HOFFMANN LA ROCHE - US5688798, 1997, A.
[7]Current Patent Assignee: HOFFMANN LA ROCHE - US5688798, 1997, A.
[8]Current Patent Assignee: NEUROGEN - WO2007/146122, 2007, A2 Location in patent: Page/Page column 42-43.
[9]Current Patent Assignee: GLAXOSMITHKLINE - US2010/222345, 2010, A1 Location in patent: Page/Page column 85.
[10]Current Patent Assignee: GLAXOSMITHKLINE - CN102516115, 2016, B Location in patent: Paragraph 0490; 0491.
[11]Current Patent Assignee: MERCK SHARP DOHME - WO2017/205193, 2017, A1 Location in patent: Page/Page column 139.
[12]Current Patent Assignee: NEUROGEN - WO2007/106349, 2007, A2 Location in patent: Page/Page column 64-65.
[13]Huang, Min; Dai, Jie; Cheng, Xu; Ding, Mengning [Organic Letters, 2019, vol. 21, # 19, p. 7759 - 7762].
  • 2
  • [ 557-21-1 ]
  • [ 158984-84-0 ]
  • [ 166398-33-0 ]
YieldReaction ConditionsOperation in experiment
With tetrakis(triphenylphosphine) palladium(0) In N,N-dimethyl-formamide at 80℃; for 0.75h; Yield given;
In N,N-dimethyl-formamide at 80℃; for 18h; 60 Example 60 t-butyl 6-cyano-3,4-dihydro-2(1H)-isoquinolinecarboxylate: To a solution of the compound (0.56 g) prepared in Example 59 in N,N-dimethylformamide (3 mL), zinc cyanide (173 mg) and tetrakis(triphenyl)phosphine palladium (173 mg) were added, followed by stirring at 80°C for 18 hours. The reaction mixture was added with a saturated aqueous sodium hydrogen carbonate solution and the mixture was extracted with t-butyl methyl ether. The organic layer was washed with water, dried and concentrated. Thus, the obtained residue was purified by silica gel column chromatography (hexane:ethyl acetate = 1:0 to 3:1) to thereby give the title compound (130 mg) having the following physical properties. TLC: Rf 0.36 (hexane:ethyl acetate = 3:1)
  • 3
  • [ 67-56-1 ]
  • [ CAS Unavailable ]
  • [ 158984-84-0 ]
  • [ 170097-66-2 ]
YieldReaction ConditionsOperation in experiment
65% With palladium diacetate; 1,3-bis-(diphenylphosphino)propane; triethylamine at 70℃;
  • 4
  • [ 111-34-2 ]
  • [ 158984-84-0 ]
  • [ 949922-27-4 ]
  • [ CAS Unavailable ]
YieldReaction ConditionsOperation in experiment
Stage #1: -butyl vinyl ether; 6-trifluoromethanesulfonyloxy-3,4-dihydro-1H-isoquinoline-2-carboxylic acid tert-butyl ester With 1,3-bis-(diphenylphosphino)propane; triethylamine In N,N-dimethyl-formamide at 80℃; for 7h; Stage #2: With water 1.IV.4 To a stirred solution of 6-trifluoromethanesulfonyloxy-3,4-dihydro-lH-isoquinoIine- 2-carboxylicacid tert-butyl ester (3.81 g, 10 mmol) in dry DMF (30 ml) are added n- butylvinyl ether (6.01 g, 60 mmol, 6.0 eq.), TEA (1.67 ml, 12 mmol, 1.2 eq.), 1,3- bis(diphenylphosphino)propane (144 mg, 0.276 mmol, 0.0276 eq.), and palladium acetate (56.1 mg, 0.25 mmol, 0.025 eq.) under nitrogen. The resulting mixture is stirred at 800C for 7 hr. Water (100 ml) is added to quench the reaction, and the mixture is extracted with EtOAc (30 ml x 3). The combined organic layer is washed with water and brine, dried over sodium sulfate, and concentrated. The crude product is purified through silica gel flash chromatography (hexane/EtOAc 10:1) to give a mixture of the vinyl ether and the ketone product, which is dissolved in EtOAc (50 ml), and then treated with concentrated hydrochloric acid (3.0 ml). The mixture is stirred at rt for 2 hr, and then basifed with saturated sodium carbonate solution. The organic phase is collected, and the aqueous phase is extracted with EtOAc twice. The combined organic phase is dried with sodium sulfate and concentrated to give the title compound. MS (+VE) m/z 176.1 (M++.).
  • 5
  • [ 158984-84-0 ]
  • [ 149104-90-5 ]
  • [ CAS Unavailable ]
YieldReaction ConditionsOperation in experiment
With sodium carbonate In 1,4-dioxane at 100℃; for 16h; 1.X.1 To a mixture of 6-trifluoromethanesulfonyloxy-3,4-dihydro-lH-isoquinoline-2- carboxylic acid t-butyl ester (350 mg, 0.92 mmol), 4-acetylphenylboronic acid (200 mg, 1.22 mmol, 1.3 eq.), Pd(PPh3)4 (8.4 mg, 0.001 mmol, 0.01 eq.) under nitrogen are added dioxane (10.0 ml) and sodium carbonate aqueous solution (2.0 N, 1.0 ml). The resulting mixture is stirred at 1000C for 16 hr. The reaction mixture is diluted with EtOAc (30 ml), washed with water and brine, dried over sodium sulfate, and concentrated. The crude product is purified through silica gel flash chromatography (hexane/EtOAc 10:1) to give the vinyl ether, which is dissolved in dioxane (10.0 ml), and then treated with concentrated hydrochloric acid (1.0 ml). The mixture is stirred at 50 0C for 1 hr, and basified with saturated sodium carbonate solution. The organic layer is collected, and the aqueous phase is extracted with EtOAc twice. The combined organic phase is dried over sodium sulfate, and concentrated to give the title compound. MS (+VE) m/z 252.1 (M+ +1).
  • 6
  • [ 158984-84-0 ]
  • [ 21043-40-3 ]
  • [ 960145-20-4 ]
YieldReaction ConditionsOperation in experiment
With 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; sodium t-butanolate In toluene at 110℃; 1.D.4 To a solution of β-trifluoromethanesulfonyloxy-S^-dihydro-lH-isoquinoline^-carboxylic acid tert- butyl ester (3.815 g, 10 mmol) in anhydrous toluene (60 ml) under nitrogen is added 1-cyclopentyl- piperazine (1.69 g, 11 mmol, 1.1 eq.), Pd(OAc)2 (56.1 mg, 0.25mmol, 0.025 eq.), BINAP (172 mg, 0.276 mmol, 0.0276 eq.), and sodium terf-butoxide (1.15 g, 12 mmol, 1.2 eq.). The resulting mixture is stirred at 110 0C overnight. After cooling to it, water (50 ml) is added to quench the reaction, and the mixture is diluted with EA (60 ml). The combined organic phase is washed with water and brine, dried over sodium sulfate, and concentrated. The crude product is purified through silica gel flash chromatography (EA / 4% TEA) to give the title compound.
  • 7
  • [ 24424-99-5 ]
  • [ 158984-84-0 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: 94 percent / Et3N / methanol / 3 h / 20 °C 2: 88 percent / pyridine / 0.17 h / 0 °C
  • 8
  • [ 63905-73-7 ]
  • [ 158984-84-0 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: 94 percent / Et3N / methanol / 3 h / 20 °C 2: 88 percent / pyridine / 0.17 h / 0 °C
  • 9
  • [ 158984-84-0 ]
  • [ 170097-67-3 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: 65 percent / Et3N; Pd(OAc)2; 1,3-bis(diphenylphosphino)propane / 70 °C 2: 99 percent / aq. NaOH / methanol; tetrahydrofuran / 3 h / Heating
  • 10
  • [ 158984-84-0 ]
  • [ 734520-80-0 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 5 steps 1.1: 65 percent / Et3N; Pd(OAc)2; 1,3-bis(diphenylphosphino)propane / 70 °C 2.1: 99 percent / aq. NaOH / methanol; tetrahydrofuran / 3 h / Heating 3.1: 95 percent / 1-hydroxybenzotriazole hydrate; Et3N; 1-(dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride / CH2Cl2 / 20 °C 4.1: 84 percent / HCl / ethanol; CH2Cl2 5.1: Et3N / CH2Cl2 / 0.25 h / 20 °C 5.2: aq. AcOH; sodium triacetoxy borohydride / CH2Cl2 / 2 h / 20 °C
 

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