1-(BENZYLOXY)-4-BROMO-2-METHOXYBENZENE

Preparation 35 Into a 250-mL round-bottom flask was placed 4-bromo-2-methoxyphenol (7.5 g, 36.94 mmol, 1.00 equiv), potassium carbonate (15 g, 108.53 mmol, 2.94 equiv), N, Ndimethylformamide (75 mL), (bromomethyl)benzene (6.5 g, 38.00 mmol, 1.03 equiv). The resulting solution was stirred for 12 h at 80 °C. The resulting solution was diluted with H20, extracted with ethyl acetate, and the organic layers combined. The resulting mixture was washed with water and brine. The solid was dried in an oven under reduced pressure. This resulted in 10.429 g (96percent) of the title compound as a light red solid.Analytical Data: ‘H NMR (300 IVIFIz, Methanol-d4) 7.48 — 7.28 (m, 5H), 7.11 (d, J 2.3 Hz, 1H), 7.01 (dd, J= 8.6, 2.3 Hz, 1H), 6.91 (d, J= 8.6 Hz, 1H), 5.09 (s, 2H), 3.85 (s, 3H).A mixture of bromo phenol 1 (10.0 g, 49.2 mmol), K4-bromo-3-methoxyphenol 6 (16.9 mmol, 3.42 g) was dissolved in anhydrousacetone (50 mL) in an oven-dried three-neck flask under argon. K2CO3 (28.8mmol, 3.97 g) was then added and the mixture was stirred for 5 minutes beforethe addition of benzyl bromide (28.8 mmol, 3.42 mL). The reaction was refluxedfor 24 h or until completion was shown by TLC (50:50 EtOAc/hexanes). Thereaction mixture was allowed to warm at room temperature, poured into saturated K2CO3 andextracted three times with EtOAc. The organic layers were combined, washed with brine, driedwith MgSO4, concentrated in vacuo and purified by silica gel column chromatography (100percenthexanes) yielding 4.54 g (92percent) of 10 as a white solid. mp = 56-58 oC. 1H-NMR (500 MHz, CDCl3): δ = 3.88 (3H, s), 5.14 (2H, s), 6.76 (1H, d, J = 8.54), 6.96-6.99 (1H, dd, J = 8.73, 6.96), 7.02 (1H, d, J = 2.5), 7.30-7.50 (5H, m). 13C-NMR (125 MHz, CDCl3): δ =56.17, 71.22, 113.39, 115.29, 115.42, 127.30, 128.00, 128.62, 136.74, 147.40, 150.51. IR (NaCl): νmax 1502, 1455, 1398, 1249, 1217, 1183, 1134, 1012, 846, 795, 746, 697 cm-1. HPLC (Retention time, percent): 27.89min, >99percent. HRMS (ESI-TOF, m/z): calcd for C14H17BrNO2 (M+NH4)+ = 310.0437, found310.0435.Preparation of 4-benzyloThe preparation of 10 has been previously reported by our group.(Step 1:

Molecular Weight:293.15
XLogP3:4
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:4
Exact Mass:292.00989
Monoisotopic Mass:292.00989
Topological Polar Surface Area:18.5
Heavy Atom Count:17
Complexity:216
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes