Diisobutylaluminum hydride → (R)-2-Chloro-6-methyl-4-morpholin-4-yl-6,7-dihydro-[1,4]dioxino[2,3-d]pyrimidine

HRID 528454Notes

Reaction equation

HRID 528454 reaction equation
C([O:3][C:4](=O)[C@H:5]([O:7][C:8]1[C:9](Cl)=[N:10][C:11]([Cl:20])=[N:12][C:13]=1[N:14]1[CH2:19][CH2:18][O:17][CH2:16][CH2:15]1)[CH3:6])C.CC(C[AlH]CC(C)C)C.[H-].[Na+]>C1COCC1>[Cl:20][C:11]1[N:12]=[C:13]([N:14]2[CH2:19][CH2:18][O:17][CH2:16][CH2:15]2)[C:8]2[O:7][C@H:5]([CH3:6])[CH2:4][O:3][C:9]=2[N:10]=1

Participants

5

Reactant 3

HCID 14487Diisobutylaluminum hydrideHCID 24758Sodium hydrideHCID 86711740(R)-2-(2,4-Dichloro-6-morpholin-4-yl-pyrimidin-5-yloxy)-propionic acid ethyl ester

Product 1

HCID 86711741(R)-2-Chloro-6-methyl-4-morpholin-4-yl-6,7-dihydro-[1,4]dioxino[2,3-d]pyrimidine

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of (R)-2-(2,4-dichloro-6-morpholin-4-yl-pyrimidin-5-yloxy)-propionic acid ethyl ester (175 mg, 0.50 mmol) in THF (5 mL) at −78° C. was added DIBAL-H (2.0 mL, 2.0 mmol, 1M solution in THF) and the resulting mixture warmed to 0° C. over 30 minutes. The reaction mixture was quenched with Rochelle's salt (1M aqueous solution) and the aqueous extracted with ethyl acetate. The combined organic extracts were dried (Na2SO4) and concentrated in vacuo. The resulting residue was taken up into THF (10 mL), to the resultant solution was added sodium hydride (60 mg, 1.50 mmol, 60% dispersion in mineral oil) and the resulting mixture stirred at RT for 18 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 affording (R)-2-Chloro-6-methyl-4-morpholin-4-yl-6,7-dihydro-[1,4]dioxino[2,3-d]pyrimidine as a white solid (157 mg, quantitative). LCMS: RT=2.89 min, [M+H]+=272/274.

Workup

  1. customThe reaction mixture was quenched with Rochelle's salt (1M aqueous solution)
  2. extractionthe aqueous extracted with ethyl acetate
  3. dry with materialThe combined organic extracts were dried (Na2SO4)
  4. concentrationconcentrated in vacuo
  5. customThe reaction mixture was quenched with saturated aqueous ammonium chloride solution
  6. extractionextracted with ethyl acetate
  7. dry with materialThe combined organic extracts were dried (Na2SO4)
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-981ee2b63dad4359b081b95f79b65b09
Source dataset
uspto-grants-2016_05
Patent number
US09346817B2

Reaction notes

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