Diethyl Ether → (R)-3-(5-bromo-2-chloropyrimidin-4-ylamino)-2-methylbutan-2-ol

HRID 1891068Notes

Reaction equation

HRID 1891068 reaction equation
CO[C:3](=O)[C@@H:4](C)[NH:5][C:6]1[C:11]([Br:12])=[CH:10][N:9]=[C:8]([Cl:13])[N:7]=1.[CH3:16][Mg]Br.[Cl-].[NH4+].C([O:23][CH2:24][CH3:25])C>C1COCC1.O>[Br:12][C:11]1[C:6]([NH:5][C@H:4]([CH3:3])[C:24]([CH3:25])([OH:23])[CH3:16])=[N:7][C:8]([Cl:13])=[N:9][CH:10]=1

Participants

7

Reactant 4

HCID 3283Diethyl EtherHCID 25517Ammonium ChlorideHCID 59674014(R)-2-(5-bromo-2-chloro-pyrimidin-4-ylamino)-propionic acid methyl esterHCID 178418573HCID 178418573, compound

Product 1

HCID 59674068(R)-3-(5-bromo-2-chloropyrimidin-4-ylamino)-2-methylbutan-2-ol

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

An ice-cooled solution of 2.95 g (10.0 mmol) of methyl-N-(5-bromo-2-chloropyrimidin-4-yl)-D-alaninate in 150 ml of THF is mixed drop by drop with 30 ml (90 mmol) of a 3 molar solution of methylmagnesium bromide in diethyl ether. After 2.5 hours at room temperature, the batch is mixed with 30 ml of saturated ammonium chloride solution. It is diluted with water and extracted from ethyl acetate (3×). The combined organic phases are dried (Na2SO4), filtered and concentrated by evaporation. The remaining residue is purified by chromatography (hexane/ethyl acetate: 4:1-1:1). 2.81 g (9.5 mmol, corresponding to 95% of theory) of the product is obtained.

Workup

  1. extractionextracted from ethyl acetate (3×)
  2. dry with materialThe combined organic phases are dried (Na2SO4)
  3. filtrationfiltered
  4. concentrationconcentrated by evaporation
  5. customThe remaining residue is purified by chromatography (hexane/ethyl acetate: 4:1-1:1)
  6. custom2.81 g (9.5 mmol, corresponding to 95% of theory) of the product is obtained

Sources & evidence

ORD record
ord-490614c1c3234a038a46b81c90792ee3
Source dataset
uspto-grants-2013_08
Patent number
US08507510B2

Reaction notes

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