Tetrabutylammonium Fluoride → 1-Cyclopropyl-2-(2,4-dichloro-6-morpholin-4-yl-pyrimidin-5-yloxy)-ethanol

HRID 528492Notes

Reaction equation

HRID 528492 reaction equation
C([Si](C)(C)[O:6][CH:7]([CH:24]1[CH2:26][CH2:25]1)[CH2:8][O:9][C:10]1[C:11]([N:18]2[CH2:23][CH2:22][O:21][CH2:20][CH2:19]2)=[N:12][C:13]([Cl:17])=[N:14][C:15]=1[Cl:16])(C)(C)C.CCCC[N+](CCCC)(CCCC)CCCC.[F-]>C1COCC1>[CH:24]1([CH:7]([OH:6])[CH2:8][O:9][C:10]2[C:15]([Cl:16])=[N:14][C:13]([Cl:17])=[N:12][C:11]=2[N:18]2[CH2:19][CH2:20][O:21][CH2:22][CH2:23]2)[CH2:26][CH2:25]1

Participants

4

Reactant 2

HCID 2724141Tetrabutylammonium FluorideHCID 867117664-{5-[2-(tert-Butyl-dimethyl-silanyloxy)-2-cyclopropyl-ethoxy]-2,6-dichloro-pyrimidin-4-yl}-morpholine

Product 1

HCID 867117671-Cyclopropyl-2-(2,4-dichloro-6-morpholin-4-yl-pyrimidin-5-yloxy)-ethanolYield 68.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 4-{5-[2-(tert-butyl-dimethyl-silanyloxy)-2-cyclopropyl-ethoxy]-2,6-dichloro-pyrimidin-4-yl}-morpholine (386 mg, 0.86 mmol) in THF (10 mL) was added TBAF (947 μL, 0.95 mmol, 1.0 M solution in THF) dropwise. The reaction mixture was stirred at RT for 3 hours before the reaction was quenched with saturated aqueous ammonium chloride solution (20 mL). The mixture was extracted with ethyl acetate (3×20 mL) and then combined organic phases were washed with brine (10 mL), dried (Na2SO4) and concentrated in vacuo. The resultant residue was purified by column chromatography (SiO2, gradient 0-50% ethyl acetate) giving 1-Cyclopropyl-2-(2,4-dichloro-6-morpholin-4-yl-pyrimidin-5-yloxy)-ethanol as a colourless gum (196 mg, 68%). LCMS: RT=3.04 min, [M+H]+=334/336.

Workup

  1. customwas quenched with saturated aqueous ammonium chloride solution (20 mL)
  2. extractionThe mixture was extracted with ethyl acetate (3×20 mL)
  3. washcombined organic phases were washed with brine (10 mL)
  4. dry with materialdried (Na2SO4)
  5. concentrationconcentrated in vacuo
  6. customThe resultant residue was purified by column chromatography (SiO2, gradient 0-50% ethyl acetate)

Sources & evidence

ORD record
ord-b0e15901a62e4e02b8d077ac46d4b27a
Source dataset
uspto-grants-2016_05
Patent number
US09346817B2

Reaction notes

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