8-Bromo-1,2,3,4-tetrahydroisoquinoline

To a solution of methanol (20 mL) and saturated sodium carbonate solution (20 mL) are added a mixture of l-(6-Bromo-3, 4-dihydro-lH-isoquinolin-2-yl)-2, 2, 2-trifluoro- ethanone and l-(8-bromo-3, 4-dihydro-lH-isoquinolin-2-yl)-2, 2, 2-trifluoro-ethanone (3 g, 9.7 mmol). The reaction mixture is refluxed overnight, concentrated and the residue is extracted with dichloromethane. The combined organic layers are washed with water and brine, dried over sodium sulfate and the solvent is evaporated. The crude product is purified by column chromatography (silica gel, 230-400 mesh) using 0-2percent methanol in chloroform as eluent to obtain 8-bromo-l, 2, 3, 4-tetrahydro-isoquinoline as colorless viscous oil (first fraction, 0.45 g, 22percent) and 6-Bromo-l, 2, 3, 4-tetrahydro-isoquinoline as white solid (second fraction, 1.0 g, 48percent). MS m/z 211.9 (M+l)NaBH3CN (30.20 g, 480.64 mmol) was added to a mixture of 8-bromoisoquinoline(20.00 g, 96.13 mmol) in MeOH (300 mL) at 0 °C. The resulting mixture was stirredfor 10 minutes and Boron trifluoride diethyl etherate (68.22 g, 480.64 mmol) was added dropwise at 0 °C. The resulting mixture was stirred for 1 hour at 0 °C and then refluxed for 4 hours. Sat. Na2CO3 (5 mL) was added and solvent was concentrated under reduced pressure. The remaining liquid was poured into water and extracted withCH2C12. The organic layer was washed with brine, dried over Mg504, filtered and evaporated in vacuo to give 20 g of intermediate 21(98percent yield) which was used in the next step without further purification.(a) 8-bromo-l, 2, 3, 4-tetrahydroisoquinoline (64 mg, 0.3 mmol) was dissolved in acetonitrile, K2C03(166 mg, 1.2 mmol) and ethyl 2-bromoacetate (40 mu^, 0.36 mmol) were added. The mixture was stirred at r.t. over night. The solvent was evaporated off, and the residue was extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated in vacuum. Purification through flash chromatography on silica gel eluted with 30percent ethyl acetate in hexane gave intermediate ethyl 2-(8-(2-chloro-4- methoxyphenyl)-3, 4-dihydroisoquinolin-2(lH)-yl)acetate 73 mg as a brown oil, yield: 86.8percent. LC/MS: (ESI) [M+H]+= 299.2

Molecular Weight:212.09
XLogP3:2
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:1
Exact Mass:210.99966
Monoisotopic Mass:210.99966
Topological Polar Surface Area:12
Heavy Atom Count:11
Complexity:138
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes