Oxalyl chloride → 3-Acetyl-2,2-dimethylcyclobutylacetic acid tert-butyl ester

HRID 432852Notes

Reaction equation

HRID 432852 reaction equation
[CH3:1][C:2]([C@H:4]1[C:7]([CH3:9])([CH3:8])[C@@H:6]([CH2:10][C:11]([OH:13])=[O:12])[CH2:5]1)=[O:3].[C:14](Cl)(=O)C(Cl)=O.CCN([CH:26]([CH3:28])[CH3:27])C(C)C>CN(C=O)C.C(O)(C)(C)C>[C:26]([O:12][C:11](=[O:13])[CH2:10][CH:6]1[CH2:5][CH:4]([C:2](=[O:3])[CH3:1])[C:7]1([CH3:8])[CH3:9])([CH3:28])([CH3:14])[CH3:27]

Participants

6

Reactant 3

HCID 65578Oxalyl chlorideHCID 81531DiisopropylethylamineHCID 7192332-[(1R,3R)-3-acetyl-2,2-dimethylcyclobutyl]acetic acid

Product 1

HCID 206090683-Acetyl-2,2-dimethylcyclobutylacetic acid tert-butyl esterYield 93%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 6386tert-ButanolSolvent

Procedure

S-Pinonic acid 5 (39.9 g, 216 mmol) was dissolved in a solution of oxalyl chloride (222 mL, 444 mmol, 2.0 M in CH2Cl2) and a few drops of DMF were then added. The solution was stirred at room temperature for 3 h, and the solvent was removed in vacuo. t-Butanol (389 mL) and DIEA (42.8 mL, 244 mmol) were added and the reaction mixture was stirred at room temperature for 16 hour before removing the solvent in vacuo. EtOAc (500 mL) was added to the slurry and was subsequently washed with H2O (500 mL) and saturated NaHCO3 (500 mL). The aqueous layers were combined and extracted with EtOAc (150 mL×2). The organic layers were combined and dried with brine and MgSO4 concentrated to yield crude 7. The oil was purified by chromatography (hexane-EtOAc, 5:1 to 4:1) to yield 7 (47.8 g, 93%) as a yellow liquid.

Workup

  1. additionwere then added
  2. customthe solvent was removed in vacuo
  3. stirringthe reaction mixture was stirred at room temperature for 16 hour
  4. custombefore removing the solvent in vacuo
  5. additionEtOAc (500 mL) was added to the slurry
  6. washwas subsequently washed with H2O (500 mL) and saturated NaHCO3 (500 mL)
  7. extractionextracted with EtOAc (150 mL×2)
  8. dry with materialdried with brine and MgSO4
  9. concentrationconcentrated
  10. customto yield crude 7
  11. customThe oil was purified by chromatography (hexane-EtOAc, 5:1 to 4:1)

Sources & evidence

ORD record
ord-1f1658f46978404e9372e14b8f973535
Source dataset
uspto-grants-2003_12
Patent number
US06664277B1

Reaction notes

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