Cesium carbonate → 4-Bromo-1-chloro-2-(4-(2-cyclopropoxyethoxy)benzyl)benzene

HRID 2038532Notes

Reaction equation

HRID 2038532 reaction equation
[Br:1][C:2]1[CH:3]=[CH:4][C:5]([Cl:16])=[C:6]([CH:15]=1)[CH2:7][C:8]1[CH:13]=[CH:12][C:11]([OH:14])=[CH:10][CH:9]=1.C([O-])([O-])=O.[Cs+].[Cs+].CC1C=CC(S(O[CH2:34][CH2:35][O:36][CH:37]2[CH2:39][CH2:38]2)(=O)=O)=CC=1>CN(C=O)C.O>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([Cl:16])=[C:6]([CH2:7][C:8]2[CH:13]=[CH:12][C:11]([O:14][CH2:34][CH2:35][O:36][CH:37]3[CH2:39][CH2:38]3)=[CH:10][CH:9]=2)[CH:15]=1

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 574237514-((5-Bromo-2-chlorophenyl)methyl)phenolHCID 59557773Toluene-4-sulfonic acid 2-cyclopropoxy-ethyl ester

Product 1

HCID 595577554-Bromo-1-chloro-2-(4-(2-cyclopropoxyethoxy)benzyl)benzeneYield 64%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A mixture of 4-(5-bromo-2-chlorobenzyl)phenol (56.7 g, 210 mmol) and Cs2CO3 (135 g, 420 mmol) in DMF (350 mL) was stirred at room temperature for 30 min, and then 2-cyclopropoxyethyl 4-methylbenzenesulfonate (crude intermediate BP from the second preceeding step above) (53.3 g, 210 mmol) was added. The reaction mixture was stirred at room temperature overnight, and then diluted with water (3 L) and extracted with EtOAc. The organic layer was washed with water, then with brine, and dried over Na2SO4. The residue was concentrated and then purified by flash column chromatography on silica gel (eluent PE:EA=10:1) to give intermediate DK as a liquid (51 g, yield 64%). 1H NMR (CDCl3, 400 MHz): δ 7.22˜7.29 (m, 3H), 7.08 (d, J=8.8 Hz, 2H), 6.88 (d, J=8.8 Hz, 2H), 4.10 (t, J=4.8 Hz, 2H), 3.86 (t, J=4.8 Hz, 2H), 3.38-3.32 (m, 1H), 0.62-0.66 (m, 2H), 0.49-0.52 (m, 2H).

Workup

  1. additionwas added
  2. stirringThe reaction mixture was stirred at room temperature overnight
  3. extractionextracted with EtOAc
  4. washThe organic layer was washed with water
  5. dry with materialwith brine, and dried over Na2SO4
  6. concentrationThe residue was concentrated
  7. custompurified by flash column chromatography on silica gel (eluent PE:EA=10:1)

Sources & evidence

ORD record
ord-5d625965792b4860ab2563e64a8c1e93
Source dataset
uspto-grants-2013_11
Patent number
US08575321B2

Reaction notes

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