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Chemical Structure| 479196-49-1 Chemical Structure| 479196-49-1

Structure of 479196-49-1

Chemical Structure| 479196-49-1

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Product Details of [ 479196-49-1 ]

CAS No. :479196-49-1
Formula : C8H9BrO2S
M.W : 249.12
SMILES Code : CC1=C(Br)C=C(C2OCCO2)S1
MDL No. :MFCD11977342

Safety of [ 479196-49-1 ]

Application In Synthesis of [ 479196-49-1 ]

* 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 [ 479196-49-1 ]

[ 479196-49-1 ] Synthesis Path-Downstream   1~2

  • 1
  • [ 60518-41-4 ]
  • [ 479196-49-1 ]
  • (1S)-7-chloro-1-[5-(1,3-dioxolan-2-yl)-2-methyl-3-thienyl]-1,2,3,4-tetrahydroisoquinoline [ No CAS ]
  • (1R)-7-chloro-1-[5-(1,3-dioxolan-2-yl)-2-methyl-3-thienyl]-1,2,3,4-tetrahydroisoquinoline [ No CAS ]
YieldReaction ConditionsOperation in experiment
50 g; 51.5 g Step 1: (lS)-7-Chloro-l-[5-(l,3-dioxolan-2-yl)-2-methyl-3-thienyl]-l,2,3,4- tetrahydroisoquinoline and (lR)-7-chloro-l-[5-(l,3-dioxolan-2-yI)-2-methyl-3-thienyl]-l,2,3,4- tetrahydroisoquinoline [00992] To a solution of 2-(4-bromo-5-methyl-2-thienyl)-l ,3-dioxolane (90.3 g, 362 mmol) in THF (500 mL) was added dropwise 2.50 M of n-BuLi ( 193 mL, 483 mmol) at -78 C under an atmosphere of N2, and the mixture was allowed to stir at -78C for 20 min. Another reaction vessel was charged with <strong>[60518-41-4]7-chloro-3,4-dihydroisoquinoline</strong> (40 g, 242 mmol) and the contents were dissolved in THF ( 1.3L). To this solution was added dropwise BF3-Et20 (32.8 mL, 265.7 mmol) at -30C, and the solution was allowed to stir for 10 min. To this mixture was added dropwise the previous lithiated mixture via cannula and the resulting mixture was allowed to stir at -30C for 30 min. Then the reaction mixture was allowed to warm to 0C and stirred for 1 h. The reaction was quenched by addition of saturated aqueous NaHC03, and the mixture was extracted with EtOAc (500 mL x 3). The combined organic layers were washed with brine, dried over Na2S04, filtered, and concentrated in vacuo. The above procedure was perfomed on the same scale two additional times. The residues from all three procedures were then combined and purified by silica gel chromagraphy, eluting with a 85/15 to 0/100 pentane/EtOAc gradient to provide a yellow solid. The resulting solid was washed with pentane of to provide the racemic mixture (1 10 g, 45%) as a yellow solid. The racemic mixture was separated into the individual component enantiomers by chiral chromatography (SFC: CHIRALPAK AD 50x300mm with 35/65 0.1 % NH4OH in MeOH/C02, 200 mL/min, 10 MPa) to obtain 51.5 g (99.7% ee) of (lR)-7- chloro- l -[5-( l ,3-dioxolan-2-yl)-2-methyl-3-thienyl]- l ,2,3,4-tetrahydroisoquinoline as first elute (retention time 3.7 min, LCMS: (AA) M+ l 336.0) and 50.0g (99.7% ee) of (l S)-7-chloro- l -[5- ( l ,3-dioxolan-2-yl)-2-methyl-3-thienyl]-l ,2,3,4-tetrahydroisoquinoline as second elute (retention time 4.8 min, LCMS: (AA) M+l 336.0).
  • 2
  • [ 60518-41-4 ]
  • [ 479196-49-1 ]
  • 7-chloro-1-[5-(1,3-dioxolan-2-yl)-2-methyl-3-thienyl]-1,2,3,4-tetrahydroisoquinoline [ No CAS ]
YieldReaction ConditionsOperation in experiment
45% Step 1: 7-Chloro-l-[5-(l,3-dioxolan-2-yl)-2-methyl-3-thienyl]-l,2,3,4-tetrahydroisoquinoline [00714] An oven-dried 2-neck 250 mL round bottom flask under nitrogen was charged with THF (40 mL) and cooled to -74 C . Added 2.50 M ra-BuLi in hexane (6.92 mL, 17.3 mmol). Added a solution of Int-1 (4.00 g, 16.0 mmol) in THF (60 mL) slowly keeping the internal temperature less than -70 C . Stirred with cooling 5 min. A second oven-dried 250 mL round bottom flask under nitrogen was charged with THF (60 mL) and Int-50 (2.04 g, 12.4 mmol) and the resulting solution was cooled to 0 C . Added boron trifluoride diethyl ether complex ( 1.71 mL, 13.6 mmol) slowly and cooled to -30 C . The contents of the first flask were transferred via cannula to the second flask. Reaction was quenched with saturated aqueous NaHC03 and warmed to rt. Water was added, and the mixture was extracted three times with EtOAc. Combined organic portions were washed with brine, dried over anhydrous Na2S04, filtered, and concentrated in vacuo. Residue was purified via flash column chromatography eluting with a hexane / EtOAc gradient (0 to 100% EtOAc) to afford the title compound as a white solid ( 1.88g, 45%). NMR (400 MHz, Chloroform-d) delta 7.17 - 7.01 (m, 2H), 6.83 - 6.61 (m, 2H), 5.92 (s, 1H), 5.09 (s, 1H), 4.17 - 4.04 (m, 2H), 4.03 - 3.92 (m, 2H), 3.37 - 3.25 (m, 1H), 3.13 - 2.91 (m, 2H), 2.82 - 2.69 (m, 1H), 2.46 (s, 3H). LCMS: (AA) M+l 336.1
 

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