Benzyltrimethylammonium dichloroiodate

YELLOW TO LIGHT BROWN CRYST. POWDER OR FLAKES Benzyltrimethylammonium dichloroiodate is a slightly brown solid and hygroscopic

To a solution of 1-[2-chloro-6-(4-chlorophenoxy)pyridin-3-yl]ethanone (2.24 g, 7.94 mmol) in dichloroethane (15.0 mL) and methanol (5.0 mL) was added benzyltrimethylammonium dichloroiodate (5.52 g, 15.9 mmol) in one portion, and the mixture was heated at 75 C for 6 h, then concentrated. The residue was taken up in ethyl acetate and water, phases separated, washed with 10% w/w aqueous Na25203, brine, dried (Mg504), andconcentrated. Flash column chromatography (heptane/ethyl acetate) yielded the desired 2-chloro- 1 -[2-chloro-6- (4-chlorophenoxy)pyridin-3-yl]ethanone (1.76 g, 62% yield, 89% pure) as a colourless oil.MS (ESI): 315.96 ([M+H]jA mixture of 1 -[6-(4-chlorophenoxy)-4-(trifluoromethyl)-3-pyridyl]ethanone (3.6 g, 11.4 mmol) and benzyltrimethylammonium dichloroiodate (7.93 g, 22.8 mmol) in 1 , 2-dichloroethane (30 mL) and methanol (10 mL) was heated to 75 C for 4 h, before the mixture was concentrated, then diluted with ethyl acetate, washedwith Na25203 (10% w/w aqueous solution), washed with brine, dried (over Mg504), concentrated, and passed over a plug of silica (heptane/ethyl acetate=85/15, 254 nm) to give 3.4 g (58% yield, 69% pure) of the target compound as a colourless oil, which was used without further purification.MS (ESI): 348.99 ([M+H]jA mixture of 1-[6-(4-chlorophenoxy)-2-(trifluoromethyl)-3-pyridyl]ethanone (8.6 g, 27.2 mmol) andbenzyltrimethylammonium dichloroiodate (18.9 g, 54.4 mmol) in 1 , 2-dichloroethane (60 mL) and methanol (20mL) was heated to 75 C for 4 h, before the mixture was concentrated, then diluted with ethyl acetate, washedwith Na25203 (10% w/w aqueous solution), washed with brine, dried (over Mg504), concentrated, and passed over a plug of silica (heptane/ethyl acetate=1/1, 254 nm) to give 8.3 g (83% yield, 96% pure) of the target compound as a pale yellow solid.MS (ESI): 348.99 ([M+H]j5.4 A solution of 3-nitro-tyrosine (1 g, 4.4 mmol, 1 eq) was dissolved in acetone:H20 (1 : 1 , 10 mL) and treated with NaHC03 (554 mg, 1.5 eq) and Boc20 (946 iL, 1 eq) and allowed to stir overnight. The reaction was acidified with 5% citric acid (pH - 3) and extracted 3x with EtOAc then the combined organic fractions were washed with brine, dried over sodium sulfate and concentrated. The crude (1.37 g, 4.2 mmol, 1 eq) was taken up in a 5:2 mixture of DCM MeOH (56 mL), treated with BTMA-IC12 (1.6 g, 1.1 eq) and NaHC03 (2.47 g, 7 eq) and allowed to stir overnight. The solid NaHCCb was then filtered, the filtrate was concentrated and acidified with 5 % citric acid (pH - 3). The aqueous layer was extracted 3x with EtOAc and the combined organic layers were dried over sodium sulfate and concentrated. The crude material (1.89 g, 4.19 mmol, 1 eq) was dissolved in acetone, and treated with K2CO3 (2.9 g, 5 eq) and Mel (1.3 mL, 5 eq) and heated to reflux over two days. The reaction mixture was then allowed to cool to room temperature, the reaction was quenched with a small amount of water and the volatiles were evaporated. 5% citric acid (pH - 3) and EtOAc were added then separated and the aqueous layer was extracted 2x with EtOAc. The combined organic layers were washed with brine, dried over sodium sulfate and concentrated. The crude material was purified via column chromatography (0-0.5% MeOH in DCM) to yield compound 5.4 (1.67 g, 82% yield over 3 steps). H NMR (CDC13, 500 MHz) delta (ppm) 7.80 (d, J = 1.5 Hz, 1H), 7.56 (d, J = 1.5 Hz, 1 H), 5.12 (d, J = 6.5 Hz, 1 H), 4.54-4.53 (m, 1H), 3.94 (s, 3H), 3.76 (s, 3H), 3.18 (dd, J = 5.0 Hz, J = 14.0 Hz, 1H) 2.98 (dd, J = 6.5 Hz, J = 14.0 Hz, 1H) 1.41 (s, 9H) 13C NMR (CDC13, 500 MHz) delta (ppm) 171.5, 155.0, 152.1 , 144.9, 143.8, 135.1, 126.4, 94.3, 80.5, 62.8, 54.2, 52.8, 37.0, 28.4. MS (ESI) m/z 503.0 (M + Na+). Compound 5.4 (127 mg, 0.27mmol, 1 eq) was then dissolved in DCM (2.5 mL) and treated with TFA (0.5 mL). When TLC analysis indicated the complete consumption of starting material the volatiles were blown off and the residue was diried under vacuum. The residue was then taken up in EtOAc and saturated NaHC03, the aqueous layer was extracted 3x with EtOAc, the combined organic layers were dried over sodium sulfate and concentrated. The resulting compound 5.6 (101 mg) was used without further purification.A stirring mixture comprised of methyl 7-fluoro-6-(2-methyl-phenylamino)-1H-benzooxazole-5-carboxylate (0.042 M), benzyltrimethylammonium dichloroiodinate (Aldrich, 95%, 0.057 M, 1.36 equiv.), and zinc chloride (0.070 M, 1.67 equiv.) in glacial acetic acid is brought to reflux for 15 minutes. The mixture is concentrated in vacuo and the residue taken up into diethyl ether. The ether solution is washed with dilute aqueous hydrochloric acid, water, and brine, is dried (MgSO4), and is concentrated in vacuo to obtain the desired product. The product may be purified by recrystallization with an appropriate solvent like ethanol.A stirring mixture comprised of methyl 7-fluoro-6-(2-methyl-phenylamino)-1H-benzoimidazole-5-carboxylate (0.2492 g, 8.326*10-4 mol), benzyltrimethylammonium dichloroiodinate (Aldrich, 95%, 0.3934 g, 0.00113 mol), and zinc chloride (0.1899 g, 0.00139 mol) in glacial acetic acid (20 ml) was brought to reflux for 15 minutes. The hot suspension was filtered to isolate the precipitate which was dried in the vacuum oven (90 C., ca. 10 mm Hg) overnight to afford 0.2392 g of a green powder; 68% yield; m.p. 219-220 C. DEC; 1H-NMR (400 MHz; DMSO) delta 8.71 (s, 1H), 8.02 (s, 1H), 7.85 (broad s, 1H), 7.43 (d, 1H, J=1.7 Hz), 7.24 (dd, 1H, J=8.5, 2.2 Hz), 6.24 (dd, 1H, J=8.5, 5.4 Hz), 3.76 (s, 3H), 2.22 (s, 3H); 19F-NMR (376 MHz; DMSO) delta -132.86 (s); MS (APCl+) 426 (M+1, 48), 169 (100); (APCl-) 424 (M-1, 100); IR (KBr) 1704, 1508, 1227 cm-1.

Benzyltrimethylammonium dichloroiodate is used in the mechanism of oxidation.

Molecular Weight:348.05
Hydrogen Bond Acceptor Count:1
Rotatable Bond Count:2
Exact Mass:346.97045
Monoisotopic Mass:346.97045
Heavy Atom Count:14
Complexity:109
Covalently-Bonded Unit Count:2
Compound Is Canonicalized:Yes