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Chemical Structure| 1398609-81-8 Chemical Structure| 1398609-81-8

Structure of 1398609-81-8

Chemical Structure| 1398609-81-8

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Product Details of [ 1398609-81-8 ]

CAS No. :1398609-81-8
Formula : C17H21NO4
M.W : 303.35
SMILES Code : O=C(N1CC2(OCC3=C2C=CC(C(C)=O)=C3)C1)OC(C)(C)C
MDL No. :MFCD27986916

Safety of [ 1398609-81-8 ]

Application In Synthesis of [ 1398609-81-8 ]

* 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 [ 1398609-81-8 ]

[ 1398609-81-8 ] Synthesis Path-Downstream   1~2

  • 1
  • [ 1190865-44-1 ]
  • [ 1398609-81-8 ]
  • [ 1398610-04-2 ]
YieldReaction ConditionsOperation in experiment
80.64% With caesium carbonate; In toluene; at 110℃; for 16h; Preparation 6: tert-butyl 5'-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-2- enoyl)-3'H-spiro[azetidi -3,1 '-isobenzofuran]-1 -carboxylate In 100 mL two neck RBF equipped with dean-stark apparatus a stirred solution of tert-butyl 5'-acetyl-3'H-spiro[azetidine-3,1 '-isobenzofuran]-1- carboxylate (Preparation 1 , 4.5g, 14.851 mmol) in toluene (13.5ml_) and trifluorotoluene (13.5ml_) was added 2,2,2-trifluoro-1 -(3,4,5-trichlorophenyl)- ethanone (4.44g, 17.079mmol) and Cs2C03 (0.483g, 1.485mmol) at room temperature. Resulting reaction mixture was heated at 1 10C for 16 hours. After complete consumption of starting material, reaction mixture was diluted with ter-butylmethyl ether (30ml_) and filtered through celite bed. Filtrate was concentrated under vacuum to afford brown sticky oil (9.01 g, crude). Crude compound was purified by column chromatography using silica gel (230-400 mesh). Desired compound was eluted in 20% ethyl acetate in n-hexane to give light yellow solid (6.54g, 80.64%). 1 H NMR (400 MHz, CDCI3)8: 1 .47 (s, 9H), 4.10 (d, J = 9.52 Hz, 2H), 4.32 (d, J = 9.36 Hz, 2H), 5.12 (s, 2 H), 7.20 (d, J = 9.76 Hz, 2H), 7.39 (s, 1 H), 7.56 (d, J = 7.96 Hz, 1 H), 7.67 (s, 1 H), 7.84 (d, J = 7.96 Hz, 1 H). LC-MS (m/z): 374.1 (M+H).
8 g With caesium carbonate; In toluene; at 110℃; for 6h;Dean-Stark; Inert atmosphere; Intermediate 4: te/f-butyl 5'-[3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-2- enoyl]-3'H-spiro[azetidine-3 1 '-isobenzofuran]-1-carboxylate The starting materials, te/f-butyl 5'-acetyl-3'H-spiro[azetidine-3, 1'-isobenzofuran]-1- carboxylate (5.5 g, 18.1 mmol), 1-(4-chloro-3,5-difluorophenyl)-2,2,2- trifluoroethanone (5.44 g, 1.15 eq), were dissolved in a solvent mixture of toluene and a,a,a-trifluorotoluene (40 ml_, 1 :1 , vol/vol) in a 100 ml_ three necked round bottom flask equipped with a Dean-Stark head and a condenser on top on one neck and a nitrogen inlet on another. The reaction mixture was heated to 1 10C and cesium carbonate (0.5 g) was added. The reaction mixture was heated for 1 h and then another 0.1 g of cesium carbonate was added and heating was continued for another 1 h under a very slow stream of nitrogen. TLC analysis showed still starting material left and another 0.1 g cesium carbonate was added and heating continued for another 1 h. This process was repeated three more times (total amount of cesium carbonate = 1.0 g, total reaction time = 6 h). The reaction mixture was cooled to room temperature, filtered through a short path of silica gel, rinsed with MTBE, and concentrated. The crude product was purified using flash silica gel column chromatography (330 g RediSep column, eluting with 0 to 20% ethyl acetate in heptanes) to yield 8 g of te/f-butyl 5'-[3-(3,5-dichloro-4-fluorophenyl)-4,4,4- trifluorobut-2-enoyl]-3'H-spiro[azetidine-3, 1'-isobenzofuran]-1-carboxylate. H-NMR (400 MHz, CDCIs) delta ppm 7.86 (d, 1 H, J = 8.0 Hz), 7.69 (s, 1 H), 7.58 (d, 1 H, J = 8.0 Hz), 7.42 (d, 1 H, J = 1.4 Hz), 7.25 (d, 2H, J = 6.1 Hz), 5.14 (s, 2H), 4.34 (d, 2H, J = 9.5 Hz), 4.13 (d, 2H, J = 9.5 Hz), 1.49 (s, 9H).
  • 2
  • [ 14401-72-0 ]
  • [ 1398609-81-8 ]
  • tert-butyl 6-[3-(3,5-dichlorophenyl)but-2-enoyl]spiro-[1H-isobenzofuran-3,3'-azetidine]-1'-carboxylate [ No CAS ]
  • tert-butyl 6-[3-(3,5-dichlorophenyl)but-2-enoyl]spiro-[1H-isobenzofuran-3,3'-azetidine]-1'-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
TiCI4 (2.91 mL, 2.91 mmol, 1 M in DCM) and tributylamine (0.76 mL, 3.17 mmol) were successively added to a stirred solution of 1 -(3,5-dichlorophenyl)ethanone (0.5 g, 2.65 mmol) in DCM (6 mL) at -78 C. After 30 minutes, tert-butyl 6-acetylspiro[1 H- isobenzofuran-3,3'-azetidine]-1 '-carboxylate (0.84g, 2.78 mmol) in DCM (2 mL) was added to the mixture at -78 C. Excess dry ice were removed and the reaction gradually warmed to -45 C and stirred between -42 C and -48 C for 1 h. Pyridine (1 .16 mL, 14.36 mmol) was added at -45 C, the cold bath removed and the reaction continued at RT overnight. It was diluted with water and extracted with DCM (3 x 50 mL), washed with brine, dried (Na2S04), filtered and evaporated. The material was purified by chromatography, 80 g cartridge, eluting with 0-20% EtOAc/Heptane to give a 1 :6 isomeric mixture of cis and trans oils. Combined yield 0.62 g (50.2 %). Trans isomer (major): 1 H NMR (400 MHz, CDCI3) delta: 7.82 (d, J= 1 .9 Hz, 2H), 7.52- 7.60 (m, 3H), 7.40 (s, 1 H), 7.01 -7.04 (m, 1 H), 5.18 (s, 2H), 4.35 (d, J=9.5 Hz, 2H), 4.17 (d, J=9.5 Hz, 2H), 2.62 (d, J=1 .2 Hz, 3H), 1 .50 (s, 9H); LCMS-ELSD tR = 2.040 min, (M+H) 418.0. Cis isomer (minor): 1 H NMR (400 MHz, CDCI3) delta: 7.62 (d, J=1 .9 Hz, 2H), 7.42 (t, J=1 .9 Hz, 1 H), 7.37 (d, J=7.8 Hz, 1 H), 7.18 (s, 1 H), 7.00 (s, 1 H), 6.64-6.68 (m, 1 H), 5.05 (s, 2H), 4.29 (d, J=9.5 Hz, 2H), 4.10 (d, J=9.6 Hz, 2H), 2.34 (d, J=1 .3 Hz, 3H), 1.48 (s, 9H); LCMS-ELSD tR = 1 .833 min, (M+H) 418.0.
 

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