3-Bromodiphenyl ether → (4-Hydroxy-4-(3-phenoxyphenyl)cyclohexane-1,1-diyl)bis(methylene) bis(4-methylbenzenesulfonate)

HRID 1855028Notes

Reaction equation

HRID 1855028 reaction equation
Br[C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([O:8][C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[CH:3]=1.[Li]CCCC.[CH3:20][C:21]1[CH:26]=[CH:25][C:24]([S:27]([O:30][CH2:31][C:32]2([CH2:39][O:40][S:41]([C:44]3[CH:49]=[CH:48][C:47]([CH3:50])=[CH:46][CH:45]=3)(=[O:43])=[O:42])[CH2:37][CH2:36][C:35](=[O:38])[CH2:34][CH2:33]2)(=[O:29])=[O:28])=[CH:23][CH:22]=1>C1COCC1>[CH3:20][C:21]1[CH:26]=[CH:25][C:24]([S:27]([O:30][CH2:31][C:32]2([CH2:39][O:40][S:41]([C:44]3[CH:45]=[CH:46][C:47]([CH3:50])=[CH:48][CH:49]=3)(=[O:43])=[O:42])[CH2:33][CH2:34][C:35]([OH:38])([C:2]3[CH:7]=[CH:6][CH:5]=[C:4]([O:8][C:9]4[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=4)[CH:3]=3)[CH2:36][CH2:37]2)(=[O:28])=[O:29])=[CH:23][CH:22]=1

Participants

5

Reactant 3

HCID 961653-Bromodiphenyl etherHCID 88538615(4-Oxocyclohexane-1,1-diyl)bis(methylene) bis(4-methylbenzenesulfonate)HCID 178418339Butyllithium

Product 1

HCID 90409620(4-Hydroxy-4-(3-phenoxyphenyl)cyclohexane-1,1-diyl)bis(methylene) bis(4-methylbenzenesulfonate)Yield 57.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

To a solution of 1-bromo-3-phenoxybenzene (0.320 g, 1.29 mmol) in anhydrous THF (10 mL) at −78° C. was added n-BuLi (0.804 mL of a 1.6 M solution in hexanes; 1.286 mmol). The reaction was stirred at −78° C. for 0.5 h and a solution of (4-oxocyclohexane-1,1-diyl)bis(methylene) bis(4-methylbenzenesulfonate) (0.5 g, 1.07 mmol) in THF (5 mL) was then added dropwise. The reaction mixture was slowly warmed to rt and stirred overnight. The reaction was quenched with sat′d aq NH4Cl and diluted with water. The mixture was extracted with EtOAc. The organic layer was dried (Na2SO4) and concentrated in vacuo. The crude oil was purified by flash chromatography on SiO2 (0 to 50% EtOAc:hexanes) to afford the title compound (0.39 g, 57% yield) as a white foam. 1H NMR (500 MHz, CDCl3) δ 7.78 (t, J=8.6 Hz, 4H), 7.41-7.33 (m, 6H), 7.29 (dd, J=11.4, 5.0 Hz, 1H), 7.16-7.10 (m, 1H), 7.08-6.99 (m, 4H), 6.89-6.84 (m, 1H), 4.01 (s, 2H), 3.81 (s, 2H), 2.49 (s, 3H), 2.45 (s, 3H), 1.75-1.47 (m, 8H).

Workup

  1. temperatureThe reaction mixture was slowly warmed to rt
  2. stirringstirred overnight
  3. customThe reaction was quenched with sat′d aq NH4Cl
  4. additiondiluted with water
  5. extractionThe mixture was extracted with EtOAc
  6. dry with materialThe organic layer was dried (Na2SO4)
  7. concentrationconcentrated in vacuo
  8. customThe crude oil was purified by flash chromatography on SiO2 (0 to 50% EtOAc:hexanes)

Sources & evidence

ORD record
ord-26e28c72872a4cc8bcce3e416754266f
Source dataset
uspto-grants-2015_02
Patent number
US08962660B2

Reaction notes

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