Sodium hydride → 7-tert-Butyl-2-chloro-4-morpholin-4-yl-6,7-dihydro-[1,4]dioxino[2,3-d]pyrimidine

HRID 528479Notes

Reaction equation

HRID 528479 reaction equation
[Cl:1][C:2]1[N:7]=[C:6](Cl)[C:5]([O:9][CH2:10][CH:11]([OH:16])[C:12]([CH3:15])([CH3:14])[CH3:13])=[C:4]([N:17]2[CH2:22][CH2:21][O:20][CH2:19][CH2:18]2)[N:3]=1.[H-].[Na+]>C1COCC1>[C:12]([CH:11]1[O:16][C:6]2[N:7]=[C:2]([Cl:1])[N:3]=[C:4]([N:17]3[CH2:22][CH2:21][O:20][CH2:19][CH2:18]3)[C:5]=2[O:9][CH2:10]1)([CH3:15])([CH3:14])[CH3:13]

Participants

4

Reactant 2

HCID 24758Sodium hydrideHCID 867117601-(2,4-Dichloro-6-morpholin-4-yl-pyrimidin-5-yloxy)-3,3-dimethyl-butan-2-ol

Product 1

HCID 867117617-tert-Butyl-2-chloro-4-morpholin-4-yl-6,7-dihydro-[1,4]dioxino[2,3-d]pyrimidineYield 109.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 1-(2,4-dichloro-6-morpholin-4-yl-pyrimidin-5-yloxy)-3,3-dimethyl-butan-2-ol (255 mg, 0.73 mmol) in THF (10 mL) was added sodium hydride (87 mg, 2.18 mmol, 60% dispersion in mineral oil) and the mixture was stirred at RT for 1.5 hours. The reaction was quenched with saturated aqueous ammonium chloride solution then extracted with ethyl acetate (×2). The combined organic layers were dried (Na2SO4) then passed through a pad of silica eluting with ethyl acetate. The relevant fractions were concentrated in vacuo giving 7-tert-Butyl-2-chloro-4-morpholin-4-yl-6,7-dihydro-[1,4]dioxino[2,3-d]pyrimidine as a white solid (250 mg, 100%). LCMS: RT=3.64 min, [M+H]+=314/316.

Workup

  1. customThe reaction was quenched with saturated aqueous ammonium chloride solution
  2. extractionthen extracted with ethyl acetate (×2)
  3. dry with materialThe combined organic layers were dried (Na2SO4)
  4. concentrationThe relevant fractions were concentrated in vacuo

Sources & evidence

ORD record
ord-483245996e154ab091759d321128718d
Source dataset
uspto-grants-2016_05
Patent number
US09346817B2

Reaction notes

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