Cesium fluoride → Methyl 3,5-bis(methoxymethoxy)-4-(2-methylallyl)benzoate

HRID 1177067Notes

Reaction equation

HRID 1177067 reaction equation
[CH3:1][O:2][C:3](=[O:19])[C:4]1[CH:9]=[C:8]([O:10][CH2:11][O:12][CH3:13])[C:7](Br)=[C:6]([O:15][CH2:16][O:17][CH3:18])[CH:5]=1.[F-].[Cs+].[CH3:22][C:23](=[CH2:38])[CH2:24][Sn](CCCC)(CCCC)CCCC>CN(C=O)C.[Cu]I.Cl[Pd]Cl.P(C(C)(C)C)(C(C)(C)C)C(C)(C)C>[CH3:1][O:2][C:3](=[O:19])[C:4]1[CH:9]=[C:8]([O:10][CH2:11][O:12][CH3:13])[C:7]([CH2:24][C:23]([CH3:38])=[CH2:22])=[C:6]([O:15][CH2:16][O:17][CH3:18])[CH:5]=1

Participants

8

Reactant 3

HCID 25953Cesium fluorideHCID 11013379Methallyltri-n-butyltinHCID 59560261Methyl 4-bromo-3,5-bis(methoxymethoxy)benzoate

Product 1

HCID 59560052Methyl 3,5-bis(methoxymethoxy)-4-(2-methylallyl)benzoateYield 125.4%

Reagents, catalysts & solvents 4

HCID 24290Palladium ChlorideCatalystHCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 83681Tris(1,1-dimethylethyl)phosphineCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
45 °C

Procedure

To a solution of 4-bromo-3,5-bis-methoxymethoxy-benzoic acid methyl ester (3h) (3.10 g, 9.25 mmol) in DMF (20 mL) was added CsF (2.80 g, 18.4 mmol), CuI (200 mg, 1.05 mmol), PdCl2 (200 mg, 1.12 mmol), 2-methylallyltributyltin (3.80, 11.0 mmol) and PtBu3 (220 mg, 1.09 mmol). The reaction mixture was degassed and heated to 45° C. overnight. The mixture was filtered through Celite, quenched with H2O (100 mL), extracted with EtOAc (2×100 mL). The organic layers were dried over MgSO4 and concentrated. The residue was purified by flash column chromatography eluting with 5% EtOAc in hexanes to give the desired product as brown oil (3.6 g) which contained tin impurities. 1H NMR (400 MHz, CDCl3) δ 7.44-7.46 (m, 2 H) 5.22 (s, 4 H) 4.61-4.76 (m, 1 H) 4.38-4.55 (m, 1 H) 3.90 (s, 3 H) 3.47 (s, 6 H) 3.42-3.45 (m, 2 H) 1.80 (s, 3 H); LCMS for C16H22O6 m/z 311.10 (M+H)+.

Workup

  1. customThe reaction mixture was degassed
  2. filtrationThe mixture was filtered through Celite
  3. customquenched with H2O (100 mL)
  4. extractionextracted with EtOAc (2×100 mL)
  5. dry with materialThe organic layers were dried over MgSO4
  6. concentrationconcentrated
  7. customThe residue was purified by flash column chromatography
  8. washeluting with 5% EtOAc in hexanes

Sources & evidence

ORD record
ord-0f606d8bdbec41f9810808aee160ced7
Source dataset
uspto-grants-2010_11
Patent number
US07842713B2

Reaction notes

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