Water → Tert-butyl 3-(trifluoromethyl)pyrrolidine-1-carboxylate

HRID 270110Notes

Reaction equation

HRID 270110 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][C:10](O)([C:13]([F:16])([F:15])[F:14])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].O=S(Cl)Cl.O>N1C=CC=CC=1>[F:16][C:13]([F:14])([F:15])[CH:10]1[CH2:11][CH2:12][N:8]([C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])[CH2:9]1

Participants

5

Reactant 3

HCID 962WaterHCID 24386Thionyl ChlorideHCID 50986427Tert-butyl 3-hydroxy-3-(trifluoromethyl)pyrrolidine-1-carboxylate

Product 1

HCID 49760526Tert-butyl 3-(trifluoromethyl)pyrrolidine-1-carboxylateYield 22.8%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

To a solution of tert-butyl3-hydroxy-3-(trifluoromethyl)pyrrolidine-1-carboxylate (468 mg, 1.83 mmol) in pyridine (10 mL) was added SOCl2 (1.71 mL) and the reaction mixture was stirred at reflux temperature under nitrogen for 25 min, cooled to room temperature, H2O (20 mL) was added, extracted with ethyl acetate. The combined organic layer was washed with dilute aqueous HCl, saturated aqueous NaHCO3 and H2O successively. The organic layer was dried over Na2SO4, filtered and concentrated. The residue was dissolved in ethanol (10 mL), Pd/C (10%) (300 mg) was added and it was hydrogenated at room temperature over the weekend. The catalyst was removed by filtration. The filtrate was concentrated in vacuo to give the subtitled compound (100 mg).

Workup

  1. temperatureat reflux temperature under nitrogen for 25 min
  2. extractionextracted with ethyl acetate
  3. washThe combined organic layer was washed with dilute aqueous HCl, saturated aqueous NaHCO3 and H2O successively
  4. dry with materialThe organic layer was dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. dissolutionThe residue was dissolved in ethanol (10 mL)
  8. additionPd/C (10%) (300 mg) was added
  9. customwas hydrogenated at room temperature over the weekend
  10. customThe catalyst was removed by filtration
  11. concentrationThe filtrate was concentrated in vacuo

Sources & evidence

ORD record
ord-a45757cebc994a8497d974fae6efc27f
Source dataset
uspto-grants-2008_11
Patent number
US07449475B2

Reaction notes

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