Methanol → 2-Bromo-3-[4-(2-methoxybenzyloxy)-benzenesulfonyl]-6-methylpyridine

HRID 1796324Notes

Reaction equation

HRID 1796324 reaction equation
[Br:1][C:2]1[C:7]([S:8]([C:11]2[CH:16]=[CH:15][C:14]([OH:17])=[CH:13][CH:12]=2)(=[O:10])=[O:9])=[CH:6][CH:5]=[C:4]([CH3:18])[N:3]=1.C([O-])([O-])=O.[K+].[K+].[CH3:25][O:26][C:27]1[CH:34]=[CH:33][CH:32]=[CH:31][C:28]=1[CH2:29]Cl.CO>CC#N.CCOC(C)=O>[Br:1][C:2]1[C:7]([S:8]([C:11]2[CH:16]=[CH:15][C:14]([O:17][CH2:29][C:28]3[CH:31]=[CH:32][CH:33]=[CH:34][C:27]=3[O:26][CH3:25])=[CH:13][CH:12]=2)(=[O:9])=[O:10])=[CH:6][CH:5]=[C:4]([CH3:18])[N:3]=1

Participants

7

Reactant 4

HCID 887MethanolHCID 11430Potassium CarbonateHCID 814952-(Chloromethyl)anisoleHCID 221816884-(2-Bromo-6-methylpyridine-3-sulfonyl)-phenol

Product 1

HCID 221816842-Bromo-3-[4-(2-methoxybenzyloxy)-benzenesulfonyl]-6-methylpyridineYield 78%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Procedure

4-(2-Bromo-6-methylpyridine-3-sulfonyl)-phenol from part E (3.22 g, 9.81 mmol), KI (1.95 g, 11.77 mmol), K2CO3 (1.63 g, 11.77 mmol), and 2-methoxybenzyl chloride (1.64 mL, 11.77 mmol) were suspended in MeCN (10 mL) and heated at reflux overnight. The mixture was cooled to rt, diluted with EtOAc, and filtered through a pad of Celite. The filtrate was concentrated and purified by column chromatography on silica gel (20% ethyl acetate in hexanes). Tritration with methanol afforded the desired product (3.44 g, 78% yield) as a colorless solid: mp 76–78° C.; 1H NMR (300 MHz, CDCl3) δ 8.43 (d, J=7.6 Hz, 1H), 7.82 (d, J=7.0 Hz, 2H), 7.31 (d, J=7.0 Hz, 1H), 7.25 (d, J=8.0 Hz, 2H), 7.01 (d, J=7.0, Hz, 2H), 6.92 (d, J=6.6 Hz, 1H), 6.85 (d, J=8.0 Hz, 1H), 5.10 (s, 2H), 3.80 (s, 3H), 2.53 (s, 3H); LRMS (APCI) m/z 448.0 [(M+H)+, calcd for C20H19NO4BrS, 448.0].

Workup

  1. temperatureheated
  2. temperatureat reflux overnight
  3. filtrationfiltered through a pad of Celite
  4. concentrationThe filtrate was concentrated
  5. custompurified by column chromatography on silica gel (20% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-77e8cc79b05c400d9090fb1b91c7389c
Source dataset
uspto-grants-2006_04
Patent number
US07030145B2

Reaction notes

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