TERT-BUTYL 7-BROMO-3,4-DIHYDROISOQUINOLINE-2(1H)-CARBOXYLATE

A. To a mixture of 7-bromo-l, 2, 3, 4-tetrahydroisoquinoline HCl salt (37 g, 150 mmol) and TEA (30 g, 300 mmol) in DCM (400 mL), Boc7 a 7-Bromo-3, 4-dihydro-1 /-/-isoquinoline-2-carboxylic acid te/f-butyl ester To 10.0 g (40.2 mmol) 7-bromo-1 , 2, 3, 4-tetrahydro-isoquinoline hydrochloride in 250 mL DCM and 50 mL (101 mmol) 2M aqueous NaTo 10.0 g (40.2 mmol) 7-bromo-1 , 2, 3, 4-tetrahydro-isoquinoline hydrochloride in 250 mL DCM and 50 mL (101 mmol) 2M aqueous NaTo a solution of 7-bromo-l, 2, 3, 4-tetrahydroisoquinoline (1 g, 4.71 mmol), NaA solution of 7-bromo-1, 2, 3, 4-tetrahydroisoquinoline (1 g, 4.71 mmol)Sodium carbonate (1 g, 9.4 mmol)Was dissolved in a mixture of tetrahydrofuran / water (16 mL / 6 mL)Boc anhydride (1.51 mL, 7.06 mmol) was added at room temperature.The reaction was stirred at room temperature overnight, diluted with water (50 mL) and extracted with ethyl acetate (50 mL x3). The combined organic phases were dried over anhydrous sodium sulfateFilter, and concentrated under reduced pressure, The title compound was obtained as a colorless oil (1.46 g, 100percent).Step 1: A solution of 7-bromo-1 , 2, 3, 4-tetrahydroisoquinoline (870 mg, 4.10 mmol) in THF (15 mL) and water (5 mL) was treated with EtzN (0.66 mL, 4.76 mmol) and di-te/f-butyl dicarbonate (940 mg, 4.31 mmol). The reaction was allowed to stir for 2 h at room temperature. The THF was removed in vacuo and the reaction mixture was taken up in water (100 mL) and extracted with EtOAc (100 mL). The organic layer was washed with a saturated NHIn a 100mL three-necked flask, 7-bromo-1, 2, 3, 4-tetrahydroisoquinoline (1g, 4.72mmol) in dichloromethane (30mL) and triethylamine (712mg, 7.04mmol) were stirred for 10 minutes. Was then added Boc2O (1.02g, 4.67mmol). The reaction mixture was stirred for 24 hours at room temperature then concentrated under reduced pressure. The residue was purified by silica gel column chromatography (petroleum ether: ethyl acetate = 20: 1) to give the product (1.1g, 75percent yield).Intermediate 26: 7-Bromo-3, 4-dihvdro-lH-isoquinoline-2-carboxylic acid tert-butyl ester; To a solution of 7-Bromo-l, 2, 3, 4-Tetrohedro-isoquinoline (4.Og 18.9mmol, leq) in dichloromethane (20 ml) were added di-t-butyl dicarbonate (4.9g, 22.5mmol) and triethylamine (4 ml, 36.4 mmol). The reaction mixture was stirred at rt for 16 hr. Aqueous sodium bicarbonate solution (150 ml) was added and the mixture was extracted with dichloromethane. The organic layer was dried over sodium sulfate, filtered, and concentrated, then the residue was purified by silica gel chromatography (0-20percent ethyl acetate in hexanes as eluant). Intermediate 26 was obtained as a clear oil (3.8g, 64.6percent). LCMS (Method 2) m/z 211.7 [MH+], Tr = 3.18 min.A mixture of 7-bromo-l, 2, 3, 4-tetrahydroisoquinoline (1.5 g, 7.07 mmol), BocGeneral procedure: Toa solution of 4a (10.0 g, 35.3 mmol)in MeOH (200 mL) was added 8M KOH solution (20 mL) and then heated to reflux.After 36 h, the reaction mixture was concentrated under reduced pressure.The mixture was diluted with H

Molecular Weight:312.20
XLogP3:3.3
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:2
Exact Mass:311.05209
Monoisotopic Mass:311.05209
Topological Polar Surface Area:29.5
Heavy Atom Count:18
Complexity:313
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes