Sodium Chloride → (2R)-2-hydroxy-3,3-dimethylbutanoic acid

HRID 1058277Notes

Reaction equation

HRID 1058277 reaction equation
N[C@H:2]([C:6]([CH3:9])([CH3:8])[CH3:7])[C:3]([OH:5])=[O:4].N([O-])=[O:11].[Na+].[Cl-].[Na+]>S(=O)(=O)(O)O.O>[CH3:7][C:6]([CH3:9])([CH3:8])[C@@H:2]([OH:11])[C:3]([OH:5])=[O:4]

Participants

6

Reactant 3

HCID 5234Sodium ChlorideHCID 6950340D-tert-leucineHCID 23668193Sodium Nitrite

Product 1

HCID 11344038(2R)-2-hydroxy-3,3-dimethylbutanoic acid

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 1118Sulfuric AcidSolvent

Procedure

To a stirred solution of (2R)-2-amino-3,3-dimethylbutyric acid (5.0 g, 38.12 mmol) in 80 mL of 1N sulfuric acid at −10° C. was dropped in slowly a solution of sodium nitrite (5.26 g, 76.23 mmol) dissolved in 25 mL of water. After addition, the reaction was allowed to slowly equilibrate to ambient temperature over 20 h. Sodium chloride (10 g) was added and the solution was extracted twice with 100 mL portions of diethyl ether. The organic layers were separated, combined, dried over anhydrous sodium sulfate, and filtered. The filtrate solvent was removed under reduced pressure. The residue was purified by preprative HPLC using a chiralpak AD column (5 cm×50 cm) using 5% ethanol in 95% hexanes with 0.2% TFA as the mobile phase at a flow rate of 80 mL/min. The product-containing fractions were concentrated in vacuo. (2R)-3,3-Dimethyl-2-hydroxybutyric acid was obtained as an oil that crystallizes on sitting (2.2 g; 44%).

Workup

  1. additionAfter addition
  2. customslowly equilibrate to ambient temperature
  3. customover 20 h
  4. extractionthe solution was extracted twice with 100 mL portions of diethyl ether
  5. customThe organic layers were separated
  6. dry with materialdried over anhydrous sodium sulfate
  7. filtrationfiltered
  8. customThe filtrate solvent was removed under reduced pressure
  9. customThe residue was purified by preprative HPLC
  10. concentrationThe product-containing fractions were concentrated in vacuo

Sources & evidence

ORD record
ord-640108256343468386b165640368cc3e
Source dataset
uspto-grants-2003_02
Patent number
US06515011B2

Reaction notes

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