Sodium hydride → 2-Chloro-7,7-dimethyl-4-morpholin-4-yl-6,7-dihydro-[1,4]dioxino[2,3-d]pyrimidine

HRID 528462Notes

Reaction equation

HRID 528462 reaction equation
[Cl:1][C:2]1[N:7]=[C:6](Cl)[C:5]([O:9][CH2:10][C:11]([CH3:14])([OH:13])[CH3:12])=[C:4]([N:15]2[CH2:20][CH2:19][O:18][CH2:17][CH2:16]2)[N:3]=1.[H-].[Na+]>C1COCC1>[Cl:1][C:2]1[N:3]=[C:4]([N:15]2[CH2:20][CH2:19][O:18][CH2:17][CH2:16]2)[C:5]2[O:9][CH2:10][C:11]([CH3:14])([CH3:12])[O:13][C:6]=2[N:7]=1

Participants

4

Reactant 2

HCID 24758Sodium hydrideHCID 867117481-(2,4-Dichloro-6-morpholin-4-yl-pyrimidin-5-yloxy)-2-methyl-propan-2-ol

Product 1

HCID 867117472-Chloro-7,7-dimethyl-4-morpholin-4-yl-6,7-dihydro-[1,4]dioxino[2,3-d]pyrimidineYield 70%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 1-(2,4-dichloro-6-morpholin-4-yl-pyrimidin-5-yloxy)-2-methyl-propan-2-ol (2.18 g, 6.77 mmol) in THF (150 mL) was added sodium hydride (812 mg, 20.31 mmol, 60% dispersion in mineral oil) and the resulting mixture stirred at RT for 5 hours. The reaction mixture was quenched with saturated aqueous ammonium chloride solution and extracted with ethyl acetate. The combined organic extracts were dried (Na2SO4) and concentrated in vacuo. The resultant residue was triturated with cyclohexane affording 2-Chloro-7,7-dimethyl-4-morpholin-4-yl-6,7-dihydro-[1,4]dioxino[2,3-d]pyrimidine as a white solid (1.35 g, 70%). LCMS: RT=3.03 min, [M+H]+=286/288.

Workup

  1. customThe reaction mixture was quenched with saturated aqueous ammonium chloride solution
  2. extractionextracted with ethyl acetate
  3. dry with materialThe combined organic extracts were dried (Na2SO4)
  4. concentrationconcentrated in vacuo
  5. customThe resultant residue was triturated with cyclohexane

Sources & evidence

ORD record
ord-0f667cdbbb4c4c648e890c925e8da116
Source dataset
uspto-grants-2016_05
Patent number
US09346817B2

Reaction notes

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