Tetrabutylammonium Fluoride → 4-((2-(3,4-Dichlorophenylamino)pyrimidin-5-yl)methoxy)phenol

HRID 77450Notes

Reaction equation

HRID 77450 reaction equation
[Si]([O:8][C:9]1[CH:31]=[CH:30][C:12]([O:13][CH2:14][C:15]2[CH:16]=[N:17][C:18]([NH:21][C:22]3[CH:27]=[CH:26][C:25]([Cl:28])=[C:24]([Cl:29])[CH:23]=3)=[N:19][CH:20]=2)=[CH:11][CH:10]=1)(C(C)(C)C)(C)C.CCCC[N+](CCCC)(CCCC)CCCC.[F-]>C1COCC1>[Cl:29][C:24]1[CH:23]=[C:22]([NH:21][C:18]2[N:17]=[CH:16][C:15]([CH2:14][O:13][C:12]3[CH:30]=[CH:31][C:9]([OH:8])=[CH:10][CH:11]=3)=[CH:20][N:19]=2)[CH:27]=[CH:26][C:25]=1[Cl:28]

Participants

4

Reactant 2

HCID 2724141Tetrabutylammonium FluorideHCID 866797345-((4-(tert-butyldimethylsilyloxy)phenoxy)methyl)-N-(3,4-dichlorophenyl)pyrimidin-2-amine

Product 1

HCID 866797364-((2-(3,4-Dichlorophenylamino)pyrimidin-5-yl)methoxy)phenolYield 36%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

5-((4-((tert-butyldimethylsilyl)oxy)phenoxy)methyl)-N-(3,4-dichlorophenyl)pyrimidin-2-amine (0.022 g, 0.046 mmol) was dissolved in THF (4.6 mL) and TBAF (0.231 ml, 0.231 mmol) was added. The mixture was stirred at room temperature for 16 h, quenched with ammonium chloride solution and extracted with ethyl acetate. The organic extract was dried over Na2SO4 and concentrated. The residue was purified by flash chromatography on silica gel using 20-50% ethyl acetate in hexanes. The desired fractions were concentrated to give 4-((2-(3,4-dichlorophenylamino)pyrimidin-5-yl)methoxy)phenol as a white solid (0.006 g, 34%). 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 8.52 (2H, s), 7.99 (1H, dd, J=1.88, 0.88 Hz), 7.33-7.45 (2H, m), 7.23 (1H, s), 6.82-6.90 (2H, m), 6.71-6.84 (2H, m), 4.91 (2H, s), 4.65 (1H, br. s.). LCMS: R.T.=1.04 min; [M+H]+=362.04

Workup

  1. customquenched with ammonium chloride solution
  2. extractionextracted with ethyl acetate
  3. extractionThe organic extract
  4. dry with materialwas dried over Na2SO4
  5. concentrationconcentrated
  6. customThe residue was purified by flash chromatography on silica gel using 20-50% ethyl acetate in hexanes
  7. concentrationThe desired fractions were concentrated

Sources & evidence

ORD record
ord-a1c5c57a6fec4b779da0a09398aa6ce1
Source dataset
uspto-grants-2014_09
Patent number
US08841301B2

Reaction notes

Loading…