Cesium carbonate → 2-{4-[4-Cyclopropyl-2-(4-trifluoromethyl-phenyl)-pyrimidin-5-ylmethoxy]-phenoxy}-2-methyl-propionic acid ethyl ester

HRID 1242465Notes

Reaction equation

HRID 1242465 reaction equation
Cl[CH2:2][C:3]1[C:4]([CH:19]2[CH2:21][CH2:20]2)=[N:5][C:6]([C:9]2[CH:14]=[CH:13][C:12]([C:15]([F:18])([F:17])[F:16])=[CH:11][CH:10]=2)=[N:7][CH:8]=1.[CH2:22]([O:24][C:25](=[O:37])[C:26]([O:29][C:30]1[CH:35]=[CH:34][C:33]([OH:36])=[CH:32][CH:31]=1)([CH3:28])[CH3:27])[CH3:23].C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C=O)C.CCOCC>[CH2:22]([O:24][C:25](=[O:37])[C:26]([O:29][C:30]1[CH:31]=[CH:32][C:33]([O:36][CH2:2][C:3]2[C:4]([CH:19]3[CH2:21][CH2:20]3)=[N:5][C:6]([C:9]3[CH:14]=[CH:13][C:12]([C:15]([F:18])([F:17])[F:16])=[CH:11][CH:10]=3)=[N:7][CH:8]=2)=[CH:34][CH:35]=1)([CH3:28])[CH3:27])[CH3:23]

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 181741Ethyl 2-(4-hydroxyphenoxy)-2-methylpropanoateHCID 219359605-Chloromethyl-4-cyclopropyl-2-(4-trifluoromethyl-phenyl)-pyrimidine

Product 1

HCID 670723982-{4-[4-Cyclopropyl-2-(4-trifluoromethyl-phenyl)-pyrimidin-5-ylmethoxy]-phenoxy}-2-methyl-propionic acid ethyl ester

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolvent

Procedure

A solution of 418 mg (1.34 mmol) 5-chloromethyl-4-cyclopropyl-2-(4-trifluoromethyl-phenyl)-pyrimidine and 300 mg (1.34 mmol) 2-(4-hydroxy-phenoxy)-2-methyl-propionic acid ethyl ester [Newman, Melvin S.; Cella, James A. Monoalkylation of hydroquinone. Journal of Organic Chemistry (1974), 39(2), p 214–15] in 5 ml DMF was treated with 523 mg (1.61 mmol) cesium carbonate. The reaction mixture was stirred 4 h at RT and then it was taken up in ether and washed with 1N HCl and water. The ether layers were concentrated under reduced pressure and the crude product was purified by chromatography over silica gel with AcOEt/heptane 1:4 giving 550 mg of pure 2-{4-[4-cyclopropyl-2-(4-trifluoromethyl-phenyl)-pyrimidin-5-ylmethoxy]-phenoxy}-2-methyl-propionic acid ethyl ester.

Workup

  1. washwashed with 1N HCl and water
  2. concentrationThe ether layers were concentrated under reduced pressure
  3. customthe crude product was purified by chromatography over silica gel with AcOEt/heptane 1:4 giving 550 mg of pure 2-{4-[4-cyclopropyl-2-(4-trifluoromethyl-phenyl)-pyrimidin-5-ylmethoxy]-phenoxy}-2-methyl-propionic acid ethyl ester

Sources & evidence

ORD record
ord-6e0c350e2e83454e9a0eb0bdaa95b00b
Source dataset
uspto-grants-2006_10
Patent number
US07115611B2

Reaction notes

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