Potassium Hydroxide → 2-{1-[(Tert-butoxy)carbonyl]-5,5-dimethylpyrrolidin-2-yl}acetic acid

HRID 387539Notes

Reaction equation

HRID 387539 reaction equation
[C:1]([O:5][C:6]([N:8]1[C:12]([CH3:14])([CH3:13])[CH2:11][CH2:10][CH:9]1[CH:15](C(OC)=O)[C:16]([O:18]C)=[O:17])=[O:7])([CH3:4])([CH3:3])[CH3:2].[OH-].[K+].CC(OC(OC(OC(C)(C)C)=O)=O)(C)C>C1COCC1.CO>[C:1]([O:5][C:6]([N:8]1[C:12]([CH3:13])([CH3:14])[CH2:11][CH2:10][CH:9]1[CH2:15][C:16]([OH:18])=[O:17])=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 3

HCID 14797Potassium HydroxideHCID 90495Di-tert-butyl dicarbonateHCID 68734273HCID 68734273, compound

Product 1

HCID 595649192-{1-[(Tert-butoxy)carbonyl]-5,5-dimethylpyrrolidin-2-yl}acetic acidYield 75%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
65 °C

Procedure

Dimethyl 2-(1-(tert-butoxycarbonyl)-5,5-dimethylpyrrolidin-2-yl)malonate (220 mg, 0.7 mmol) was placed in 1:1 THF:MeOH (3 mL). KOH (0.8 mL, 1.7 mmol) was then added, and the reaction heated to 65° C. for 6 hours. The reaction was then cooled to room temperature and concentrated to remove the THF and MeOH. The reaction was then acidified with 6M HCl and then heated to 85° C. overnight to achieve decarboxylation. The reaction was then cooled to room temperature and basicified with solid NaOH until a pH of 14. THF (10 mL) and Boc2O (5 equivalents) were then added. The reaction was stirred for 20 hours at 50° C. and then cooled to room temperature. The reaction was extracted with DCM, and the organic fraction was discarded. The aqueous fraction was then acidified to a pH of 2 with 10% aqueous citric acid and then extracted with DCM. The combined organic fractions were dried, filtered, and concentrated to give the product 2-(1-(tert-butoxycarbonyl)-5,5-dimethylpyrrolidin-2-yl)acetic acid (130 mg, 75% yield).

Workup

  1. temperatureThe reaction was then cooled to room temperature
  2. concentrationconcentrated
  3. customto remove the THF and MeOH
  4. temperatureheated to 85° C. overnight
  5. temperatureThe reaction was then cooled to room temperature and basicified with solid NaOH until a pH of 14
  6. temperaturecooled to room temperature
  7. extractionThe reaction was extracted with DCM
  8. extractionextracted with DCM
  9. customThe combined organic fractions were dried
  10. filtrationfiltered
  11. concentrationconcentrated

Sources & evidence

ORD record
ord-481dfec3a06146d5b48641a0264e6a33
Source dataset
uspto-grants-2013_02
Patent number
US08372842B2

Reaction notes

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