Isopropyl iodide → Ethyl {3-methoxy-4-[(propan-2-yl)oxy]phenyl}acetate

HRID 868898Notes

Reaction equation

HRID 868898 reaction equation
[CH2:1]([O:3][C:4](=[O:17])[CH:5](CC)[C:6]1[CH:11]=[CH:10][C:9]([OH:12])=[C:8]([O:13][CH3:14])[CH:7]=1)[CH3:2].C([O-])([O-])=O.[K+].[K+].I[CH:25]([CH3:27])[CH3:26]>CN(C=O)C.CCOC(C)=O>[CH2:1]([O:3][C:4](=[O:17])[CH2:5][C:6]1[CH:11]=[CH:10][C:9]([O:12][CH:25]([CH3:27])[CH3:26])=[C:8]([O:13][CH3:14])[CH:7]=1)[CH3:2]

Participants

6

Reactant 3

HCID 6362Isopropyl iodideHCID 11430Potassium CarbonateHCID 23087680HCID 23087680, compound

Product 1

HCID 58438018Ethyl {3-methoxy-4-[(propan-2-yl)oxy]phenyl}acetateYield 89%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
60 °C

Procedure

A mixture of ethyl (4-hydroxy-3-methoxy-phenyl)-acetic acid ethyl ester (11.22 g, 53.4 mmol) and K2CO3 (22.13 g, 160 mmol) in DMF (100 ml) was heated at 60° C. 2-Iodopropane (9.06 ml, 91 mmol) was added and the mixture was vigorously stirred at 60° C. for 5 h. The reaction mixture was cooled to RT, diluted with AcOEt and washed with water. The aqueous phase was separated and further extracted with AcOEt. The combined organic fractions were dried over Na2SO4, filtered and evaporated to dryness. The resulting crude material was purified by Combi-Flash Companion™ (Isco Inc.) column chromatography (SiO2; gradient elution, heptane/AcOEt 98:2→3:1) to yield the title compound (11.94 g, 47.3 mmol, 89%) as a colorless oil. TLC: RF=0.44 (heptane/AcOEt 7:3); HPLC: AtRet=2.14 min; LC-MS: m/z 253.4 [M+H]+; 1H NMR (400 MHz, CDCl3): 1.28 (t, J=7.1, 3H), 1.38 (d, J=6.1, 6H), 3.56 (s, 2H), 3.87 (s, 3H), 4.17 (q, J=7.1, 2H), 4.50 (h, J=6.1, 1H), 6.77-6.89 (m, 3H).

Workup

  1. temperatureThe reaction mixture was cooled to RT
  2. washwashed with water
  3. customThe aqueous phase was separated
  4. extractionfurther extracted with AcOEt
  5. dry with materialThe combined organic fractions were dried over Na2SO4
  6. filtrationfiltered
  7. customevaporated to dryness
  8. customThe resulting crude material was purified by Combi-Flash Companion™ (Isco Inc.) column chromatography (SiO2; gradient elution, heptane/AcOEt 98:2→3:1)

Sources & evidence

ORD record
ord-ca18e6bd9341415d9199b830ed9311b7
Source dataset
uspto-grants-2015_03
Patent number
US08969351B2

Reaction notes

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