Potassium Carbonate → Ethyl {2-[2-acetyl-5-(quinolin-2-ylmethoxy)-phenoxymethyl]-6-methyl-phenoxy}-acetate

HRID 892183Notes

Reaction equation

HRID 892183 reaction equation
[OH:1][C:2]1[CH:7]=[C:6]([O:8][CH2:9][C:10]2[CH:19]=[CH:18][C:17]3[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=3)[N:11]=2)[CH:5]=[CH:4][C:3]=1[C:20](=[O:22])[CH3:21].Br[CH2:24][C:25]1[CH:37]=[CH:36][CH:35]=[C:34]([CH3:38])[C:26]=1[O:27][CH2:28][C:29]([O:31][CH2:32][CH3:33])=[O:30].C([O-])([O-])=O.[K+].[K+]>CN(C=O)C.C(#N)C>[C:20]([C:3]1[CH:4]=[CH:5][C:6]([O:8][CH2:9][C:10]2[CH:19]=[CH:18][C:17]3[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=3)[N:11]=2)=[CH:7][C:2]=1[O:1][CH2:24][C:25]1[CH:37]=[CH:36][CH:35]=[C:34]([CH3:38])[C:26]=1[O:27][CH2:28][C:29]([O:31][CH2:32][CH3:33])=[O:30])(=[O:22])[CH3:21]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 222414811-[2-Hydroxy-4-(quinolin-2-ylmethoxy)-phenyl]-ethanoneHCID 53945283Ethyl (2-bromomethyl-6-methyl-phenoxy)-acetate

Product 1

HCID 53728390Ethyl {2-[2-acetyl-5-(quinolin-2-ylmethoxy)-phenoxymethyl]-6-methyl-phenoxy}-acetate

Reagents, catalysts & solvents 1

HCID 21891449acetonitrile N,N-dimethylformamideSolvent

Conditions

Temperature
50 °C

Procedure

1-[2-Hydroxy-4-(quinolin-2-ylmethoxy)-phenyl]-ethanone (185 mg, 0.63 mmol, example 58) is dissolved in 2:1 DMF/acetonitrile (6 mL). Ethyl (2-bromomethyl-6-methyl-phenoxy)-acetate (272 mg, 0.95 mmol, example 43b) and K2CO3 (177 mg, 1.26 mmol) are added and the contents are heated to 50° C. for 2 days. The reaction is cooled to r.t. and the volume reduced under a nitrogen stream at 40° C. The contents are partitioned between ethyl acetate (50 mL) and water (50 mL). The aqueous layer is further extracted with ethyl acetate (2×50 mL). The organic fractions are combined and washed with brine (3×75 mL), dried over MgSO4 and concentrated. The crude material is dissolved in 1:1 dichloromethane/methanol, preadsorbed onto silica gel, and purified by flash chromatography (silica, 20% ethyl acetate in hexanes) to give the title compound. MS (ion spray) 500 (M+H)+.

Workup

  1. temperatureThe reaction is cooled to r.t.
  2. customat 40° C
  3. customThe contents are partitioned between ethyl acetate (50 mL) and water (50 mL)
  4. extractionThe aqueous layer is further extracted with ethyl acetate (2×50 mL)
  5. washwashed with brine (3×75 mL)
  6. dry with materialdried over MgSO4
  7. concentrationconcentrated
  8. dissolutionThe crude material is dissolved in 1:1 dichloromethane/methanol
  9. custompurified by flash chromatography (silica, 20% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-af17131100dc4a888c8340d7639df479
Source dataset
uspto-grants-2006_02
Patent number
US07005440B1

Reaction notes

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