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

HRID 1859405Notes

Reaction equation

HRID 1859405 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>[OH:11][C@H:2]([C:6]([CH3:9])([CH3:8])[CH3:7])[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 2(R)-amino-3,3-dimethylbutyric acid (5.0 g, 38.1 mmol) in 80 mL of 1 N sulfuric acid at −10° C. was slowly added a solution of sodium nitrite (5.26 g, 76.2 mmol) dissolved in 25 mL of water. After the addition was complete, the reaction was gradually warmed to ambient temperature and stirred for 20 h. Sodium chloride (10 g) was added and the solution was extracted twice with 100 mL portions of ether. The combined organic layers were dried over anhydrous sodium sulfate and filtered. The filtrate solvent was removed under reduced pressure. The residue was purified by preparative 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. 2(R)-Hydroxy-3,3-dimethylbutanoic acid was obtained as an oil that crystallized on standing (2.2 g; 44%); 1H NMR, 400 MHz, CDCl3, 6.0-7.0 ppm (v br s, 2H), 3.91 ppm (s, 1H), 1.03 ppm (s, 9H).

Workup

  1. additionAfter the addition
  2. extractionthe solution was extracted twice with 100 mL portions of ether
  3. dry with materialThe combined organic layers were dried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. customThe filtrate solvent was removed under reduced pressure
  6. customThe residue was purified by preparative HPLC
  7. concentrationThe product-containing fractions were concentrated in vacuo

Sources & evidence

ORD record
ord-1176777bbbf34726ab26ce98f05ad528
Source dataset
uspto-grants-2003_03
Patent number
US06528503B2

Reaction notes

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