1,4-Dioxane → 2-(4-morpholinyl)-5-Pyrimidinol

HRID 1021216

Reaction equation

HRID 1021216 reaction equation
Br[C:2]1[CH:3]=[N:4][C:5]([N:8]2[CH2:13][CH2:12][O:11][CH2:10][CH2:9]2)=[N:6][CH:7]=1.CC1(C)C(C)(C)OB(B2OC(C)(C)C(C)(C)O2)[O:16]1.C([O-])(=O)C.[K+].O1CCOCC1>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.CCOC(C)=O.O>[N:8]1([C:5]2[N:4]=[CH:3][C:2]([OH:16])=[CH:7][N:6]=2)[CH2:13][CH2:12][O:11][CH2:10][CH2:9]1

Participants

8

Reactant 4

HCID 312751,4-DioxaneHCID 517044Potassium AcetateHCID 2733548Bis(pinacolato)diboraneHCID 51443624-(5-Bromopyrimidin-2-yl)morpholine

Product 1

HCID 198710352-(4-morpholinyl)-5-PyrimidinolYield 41.1%

Reagents, catalysts & solvents 3

HCID 178418476HCID 178418476, compoundCatalystHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 4-(5-bromopyrimidin-2-yl)morpholine (2 g), 4,4,4′,4′,5,5,5′,5′-octamethyl-2,2′-bi-1,3,2-dioxaborolane (2.5 g), bis(triphenylphosphine)palladium chloride (180 mg), potassium acetate (2.5 g), and dioxane (20 ml) was stirred at 80° C. overnight under argon atmosphere. Water and EtOAc were added to the reaction mixture, and the organic layer was dried over MgSO4 and concentrated under reduced pressure. The obtained residue was mixed with THF (10 ml) and water (10 ml), and sodium perborate.tetrahydrate (3.5 g) was added thereto, followed by stirring at room temperature overnight. Then, a saturated aqueous ammonium chloride solution was added thereto. The aqueous layer was extracted with EtOAc, and the organic layer was dried over MgSO4 and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (hexane/EtOAc) to obtain 2-(morpholin-4-yl)pyrimidin-5-ol (610 mg).

Workup

  1. dry with materialthe organic layer was dried over MgSO4
  2. concentrationconcentrated under reduced pressure
  3. additionThe obtained residue was mixed with THF (10 ml) and water (10 ml), and sodium perborate
  4. additiontetrahydrate (3.5 g) was added
  5. stirringby stirring at room temperature overnight
  6. additionThen, a saturated aqueous ammonium chloride solution was added
  7. extractionThe aqueous layer was extracted with EtOAc
  8. dry with materialthe organic layer was dried over MgSO4
  9. concentrationconcentrated under reduced pressure
  10. customThe obtained residue was purified by silica gel column chromatography (hexane/EtOAc)

Sources & evidence

ORD record
ord-0113e6ff68014374a71b35e65f9ae46c
Source dataset
uspto-grants-2014_05
Patent number
US08716470B2

Linked notes

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