5-(BROMOMETHYL)-2,3-DIHYDRO-1,4-BENZODIOXINE,97%

A solution of 20 (3.75 g, 32.3 mmol) in diethyl ether (80 mL) was cooled to 0 °C and phosphorous tribromide (3.67 mL, 38.8 mmol) was added dropwise. The solution was stirred at 0 °C for 10 min, then at r.t. for 1 h. Water (10 mL) was added cautiously to quench the excess of reagent and the mixture was diluted with diethyl ether and washed with water (3 x 50 mL). The combined organic layers were washed with brine (100 mL), dried over NaA solution of the above alcohol (3.75 g, 32.3 mmol) in Et2O (80mL) was cooled to 0 C and phosphorous tribromide (3.67 mL, 38.8mmol) was added dropwise. The solution was stirred at 0 C for 10min, then at 20 C for 1 h. Water (10 mL) was added cautiously toquench the excess of reagent and the mixture was diluted withdiethyl ether and washed with water (3 50 mL). The combinedorganic layers were washed with brine (100 mL), dried over Na2-SO4, filtered and concentrated under reduced pressure to obtain5-(bromomethyl)-2, 3-dihydrobenzo[b][1, 4]dioxine as a brownsolid (4.61 g, 62percent). 1H NMR (CDCl3, 400 MHz) d 6.91–6.77 (m, 3H), 4.52 (s, 2H), 4.35–4.33 (m, 2H), 4.29–4.27 (m, 2H). Found:[M+H-Br] = 149.5.A mixture of 1 (4.42 g, 15.4 mmol), 21 (4.6 g, 20.0 mmol) and Cs2C03 (11.54 g, 0.77 mmol) in toluene:DMF (60 mL, 2: 1) was degassed under N2, then Pd(PPh3)4 (0.890 g, 0.77 mmol) was added, and the mixture heated at 110 C for 4 h. The mixture was cooled to r.t., filtered through a plug of Celite, water (150 mL) was added and extracted with EtOAc (3 x 100 mL). The combined organic layers were washed with brine (100 mL), dried over Na2S04, filtered and concentrated under reduced pressure to obtain a yellow residue. Purification by flash column chromatography using hexanes:EtOAc (9: 1) gave 22 as white solid (3.1 g, 52%). 1H MR (CDC13) delta 7.75 (d, J = 2.2 Hz, 1H), 7.73-7.70 (m, 1H), 7.61-7.59 (m, 1H), 7.43 (s, 1H), 6.84-6.78 (m, 2H), 6.72-6.70 (m, 1H), 4.27-4.22 (m, 4H), 4.10 (s, 3H), 3.98 (s, 2H). Found: [M+H]=386.6A mixture of the above bromide (4.6 g, 20.0 mmol), (6-bromo-2-methoxyquinolin-3-yl)boronic acid (V) (4.42 g, 15.4 mmol) andCs2CO3 (11.54 g, 0.77 mmol) in toluene:DMF (60 mL, 2:1) wasdegassed under N2, then Pd(PPh3)4 (0.890 g, 0.77 mmol) wasadded, and the mixture heated at 110 C for 4 h. The mixture wascooled to 20 C, filtered through a plug of Celite, water (150 mL)was added and extracted with EtOAc (3 100 mL). The combinedorganic layers were washed with brine (100 mL), dried over Na2-SO4, filtered and concentrated under reduced pressure to obtain ayellow residue. Purification by flash column chromatography usinghexanes:EtOAc (9:1) gave 6-bromo-3-((2, 3-dihydrobenzo[b][1, 4]-dioxin-5-yl)methyl)-2-methoxyquinoline (VI: Y = 2, 3-O(CH2)2O-)as white solid (3.1 g, 52%). 1H NMR (CDCl3) d 7.75 (d, J = 2.2 Hz, 1H), 7.73-7.70 (m, 1H), 7.61-7.59 (m, 1H), 7.43 (s, 1H), 6.84-6.78 (m, 2H), 6.72-6.70 (m, 1H), 4.27-4.22 (m, 4H), 4.10 (s, 3H), 3.98 (s, 2H). Found: [M+H] = 386.6.A solution of 20 (3.75 g, 32.3 mmol) in diethyl ether (80 mL) was cooled to 0 C and phosphorous tribromide (3.67 mL, 38.8 mmol) was added dropwise. The solution was stirred at 0 C for 10 min, then at r.t. for 1 h. Water (10 mL) was added cautiously to quench the excess of reagent and the mixture was diluted with diethyl ether and washed with water (3 x 50 mL). The combined organic layers were washed with brine (100 mL), dried over Na2S04, filtered and concentrated under reduced pressure to obtain 21 as a brown solid (4.61 g, 62%). 1H NMR (CDCI3) delta 6.91-6.77 (m, 3H), 4.52 (s, 2H), 4.35-4.33 (m, 2H), 4.29-4.27 (m, 2H). Found: [M+H- Br]=149.5.A solution of the above alcohol (3.75 g, 32.3 mmol) in Et2O (80mL) was cooled to 0 C and phosphorous tribromide (3.67 mL, 38.8mmol) was added dropwise. The solution was stirred at 0 C for 10min, then at 20 C for 1 h. Water (10 mL) was added cautiously toquench the excess of reagent and the mixture was diluted withdiethyl ether and washed with water (3 50 mL). The combinedorganic layers were washed with brine (100 mL), dried over Na2-SO4, filtered and concentrated under reduced pressure to obtainStep A 5-Formyl-2, 3-dihydro-1, 4-benizodioxin The procedure is as for Step A of Preparation 1. The cyclised product is purified over a silica column eluted with a 3:7 AcOEt/PE mixture. Melting point: 61 C.

Molecular Weight:229.07
XLogP3:2.2
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:1
Exact Mass:227.97859
Monoisotopic Mass:227.97859
Topological Polar Surface Area:18.5
Heavy Atom Count:12
Complexity:152
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes