Potassium Carbonate → 3-[3-Chloro-4-(cyclopropylmethoxy)phenyl]-1-cyclopentylpropan-1-one

HRID 1453192Notes

Reaction equation

HRID 1453192 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH2:9][CH2:10][C:11]([CH:13]2[CH2:17][CH2:16][CH2:15][CH2:14]2)=[O:12])[CH:5]=[CH:6][C:7]=1[OH:8].CN(C=O)C.CC#N.C([O-])([O-])=O.[K+].[K+].Br[CH2:33][CH:34]1[CH2:36][CH2:35]1>CN(C=O)C>[Cl:1][C:2]1[CH:3]=[C:4]([CH2:9][CH2:10][C:11]([CH:13]2[CH2:17][CH2:16][CH2:15][CH2:14]2)=[O:12])[CH:5]=[CH:6][C:7]=1[O:8][CH2:33][CH:34]1[CH2:36][CH2:35]1

Participants

6

Reactant 4

HCID 11430Potassium CarbonateHCID 81503BromomethylcyclopropaneHCID 21891449acetonitrile N,N-dimethylformamideHCID 587626963-(3-Chloro-4-hydroxyphenyl)-1-cyclopentylpropan-1-one

Product 1

HCID 587622103-[3-Chloro-4-(cyclopropylmethoxy)phenyl]-1-cyclopentylpropan-1-oneYield 96%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

A solution of 3-(3-chloro-4-hydroxyphenyl)-1-cyclopentylpropan-1-one ((25 g, 0.099 mol, from Step 2) in 1:1 DMF/CH3CN (200 mL) was treated with K2CO3 (15 g, 0.109 mol, 1.1 equiv), and the mixture stirred for 15 min. A solution of (bromomethyl)cyclopropane (17.4 g, 0.129 mol, 1.3 equiv) in DMF (50 mL) was added dropwise, and the reaction mixture heated to 100° C. for 1 h. The volatiles were removed in vacuo. The residue was dissolved in a minimal amount of ethyl acetate, and this solution washed with water, dried over Na2SO4, filtered, and evaporated. Chromatographic purification of the residue on silica gel using hexanes/ethyl acetate afforded 29.12 g (96%) of the title compound. 1H NMR (CDCl3) δ 0.32 (m, 2H), 0.58 (m, 2H), 1.23 (m, 1H), 1.64 (m, 8H), 2.70 (m, 5H), 3.8 (d, J=6 Hz, 2H), 6.78 (d, J=9 Hz, 1H), 6.93 (d, J=9 Hz, 1H), 7.13 (s, 1H). MS calcd for C18H23ClO2, 306.83, found [M+1)]: 307.0

Workup

  1. customThe volatiles were removed in vacuo
  2. dissolutionThe residue was dissolved in a minimal amount of ethyl acetate
  3. washthis solution washed with water
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. customevaporated
  7. customChromatographic purification of the residue on silica gel

Sources & evidence

ORD record
ord-350733605f6a46d8abfd954eb1b5c5fc
Source dataset
uspto-grants-2009_01
Patent number
US07473790B2

Reaction notes

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