Hydrogen Peroxide → (R)-4-(tert-Butoxy)-2-(cyclopentylmethyl)-4-oxobutanoic acid

HRID 15274Notes

Reaction equation

HRID 15274 reaction equation
[C:1]([O:5][C:6](=[O:30])[CH2:7][C@@H:8]([CH2:24][CH:25]1[CH2:29][CH2:28][CH2:27][CH2:26]1)[C:9](N1[C@@H](CC2C=CC=CC=2)COC1=O)=[O:10])([CH3:4])([CH3:3])[CH3:2].OO.[Li+].[OH-].S([O-])([O-])=[O:36].[Na+].[Na+].C(=O)(O)[O-].[Na+]>C1COCC1.O>[C:1]([O:5][C:6](=[O:30])[CH2:7][C@@H:8]([CH2:24][CH:25]1[CH2:29][CH2:28][CH2:27][CH2:26]1)[C:9]([OH:10])=[O:36])([CH3:2])([CH3:3])[CH3:4]

Participants

8

Reactant 5

HCID 784Hydrogen PeroxideHCID 3939Lithium HydroxideHCID 24437Sodium SulfiteHCID 516892Sodium BicarbonateHCID 9931682HCID 9931682, compound

Product 1

HCID 9816539(R)-4-(tert-Butoxy)-2-(cyclopentylmethyl)-4-oxobutanoic acidYield 73%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

4-(4-(S)-Benzyl-2-oxo-oxazolidin-3-yl)-3-(R)-cyclopentylmethyl-4-oxo-butyric acid tert-butyl ester (620 mg, 1.49 mmol, 1.0 eq.) was dissolved in THF (35 mL) and cooled in a 0° C. ice-water bath. Hydrogen peroxide (31 w/w %) (654 μL, 5.97 mmol, 4.0 eq.) and LiOH (72 mg, 2.98 mmol, 2.0 eq.) in water (7.5 mL) was added to the reaction mixture. The reaction stirred at 0° C. and judged to completion by LC/MS. Saturated sodium sulfite (18 mL) and sodium bicarbonate (18 mL) is added to the reaction. THF was evaporated by rotary evaporation and extracted the aqueous layer with CH2Cl2 (3×75 mL) to remove the chiral auxiliary. The aqueous layer was acidified at 0° C. with 6M HCl to pH˜1 and extracted with ethyl acetate (4×75 mL). The combined organic extracts were dried over MgSO4, filtered and evaporated to provide 281 mg (1.10 mmol, 73%) of 2-(R)-Cyclopentylmethyl-succinic acid 4-tert-butyl ester as clear oil and used directly in Step B. HPLC-MS calcd. for C14H24O4 (M+Na+) 279.3, found 279.3.

Workup

  1. customTHF was evaporated by rotary evaporation
  2. extractionextracted the aqueous layer with CH2Cl2 (3×75 mL)
  3. customto remove the chiral auxiliary
  4. customwas acidified at 0° C. with 6M HCl to pH˜1
  5. extractionextracted with ethyl acetate (4×75 mL)
  6. dry with materialThe combined organic extracts were dried over MgSO4
  7. filtrationfiltered
  8. customevaporated

Sources & evidence

ORD record
ord-f1614fe8ad594ea9b7ff9667cbc494c1
Source dataset
uspto-grants-2010_06
Patent number
US07732449B2

Reaction notes

Loading…