Diisobutylaluminumhydride → (R)-2-((5-Bromo-2-chloropyrimidin-4-yl)amino)propanal

HRID 1891069Notes

Reaction equation

HRID 1891069 reaction equation
C[O:2][C:3](=O)[C@@H:4]([CH3:14])[NH:5][C:6]1[C:11]([Br:12])=[CH:10][N:9]=[C:8]([Cl:13])[N:7]=1.[H-].C([Al+]CC(C)C)C(C)C>C1(C)C=CC=CC=1>[Br:12][C:11]1[C:6]([NH:5][C@H:4]([CH3:14])[CH:3]=[O:2])=[N:7][C:8]([Cl:13])=[N:9][CH:10]=1

Participants

4

Reactant 2

HCID 21225700DiisobutylaluminumhydrideHCID 59674014(R)-2-(5-bromo-2-chloro-pyrimidin-4-ylamino)-propionic acid methyl ester

Product 1

HCID 59674036(R)-2-((5-Bromo-2-chloropyrimidin-4-yl)amino)propanal

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

A solution of 40.0 g (135.8 mmol) of methyl-N-(5-bromo-2-chloropyrimidin-4-yl)-D-alaninate in 800 ml of toluene is mixed at −78° C. with 310 ml of a 1.2 molar solution of diisobutyl aluminum hydride. After 30 minutes, it is carefully quenched with methanol. The batch is heated to room temperature and diluted with 1000 ml of tert-butyl methyl ether. It is washed successively with 1N HCl (3×100 ml), saturated sodium bicarbonate solution (3×) and saturated NaCl solution (3×). The organic phase is dried (MgSO4), filtered and concentrated by evaporation. The remaining residue is purified by chromatography (hexane/ethyl acetate: 4:1-1:1). 22.5 g (83.9 mmol, corresponding to 62% of theory) of the product is obtained.

Workup

  1. customit is carefully quenched with methanol
  2. additiondiluted with 1000 ml of tert-butyl methyl ether
  3. washIt is washed successively with 1N HCl (3×100 ml), saturated sodium bicarbonate solution (3×) and saturated NaCl solution (3×)
  4. dry with materialThe organic phase is dried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated by evaporation
  7. customThe remaining residue is purified by chromatography (hexane/ethyl acetate: 4:1-1:1)
  8. custom22.5 g (83.9 mmol, corresponding to 62% of theory) of the product is obtained

Sources & evidence

ORD record
ord-baef29a25a9048d08352923b1ca1c28a
Source dataset
uspto-grants-2013_08
Patent number
US08507510B2

Reaction notes

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