Ethyl 1-benzyl-4-(trifluoromethyl)pyrrolidine-3-carboxylate → [1-Benzyl-4-(trifluoromethyl)pyrrolidin-3-yl]methanol

HRID 842227Notes

Reaction equation

HRID 842227 reaction equation
[CH2:1]([N:8]1[CH2:12][CH:11]([C:13]([F:16])([F:15])[F:14])[CH:10]([C:17](OCC)=[O:18])[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[H-].[H-].[H-].[Li+].[Al+3]>C1COCC1>[CH2:1]([N:8]1[CH2:12][CH:11]([C:13]([F:16])([F:14])[F:15])[CH:10]([CH2:17][OH:18])[CH2:9]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

4

Reactant 2

HCID 18388374Ethyl 1-benzyl-4-(trifluoromethyl)pyrrolidine-3-carboxylateHCID 21226445Aluminium lithium hydride

Product 1

HCID 18388364[1-Benzyl-4-(trifluoromethyl)pyrrolidin-3-yl]methanolYield 96.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 1.8 g (6 mmol) of 1-benzyl-3-(RS)-carboethoxy-4-(RS)-trifluoromethylpyrrolidine in 20 mL of THF at 0° C. was added 4.8 mL (4.8 mmol) of a 1M solution of LAH in THF and the reaction was stirred at rt for 30 min. The reaction mixture was quenched with 5N NaOH solution and extracted with ether. The combined organic fractions were washed with 2N NaOH solution and sat'd NaCl solution, dried over Na2SO4, filtered and the filtrate was concentrated. The residue was purified by chromatography (silica, acetone:hexanes, 1:8) to give 1.5 g of the title compound. 1H NMR (CDCl3) δ (key peaks) 7.28-7.37 (m, 5H), 3.76 (d of d, 1H, J=3.5, 10.5 Hz), 3.63 (s, 2H), 3.62 (d of d, 1H, J=5.0, 10.5 Hz), 3.11 (t, 1H, J=9.0 Hz), 2.60 (t, 1H, J=7.0 Hz), 2.45-2.49 (m, 1H), 2.42 (d of d, 1H, J=7.5, 9.5 Hz).

Workup

  1. customThe reaction mixture was quenched with 5N NaOH solution
  2. extractionextracted with ether
  3. washThe combined organic fractions were washed with 2N NaOH solution
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationthe filtrate was concentrated
  7. customThe residue was purified by chromatography (silica, acetone:hexanes, 1:8)

Sources & evidence

ORD record
ord-bc45592bf5fa4dfe86aecbde29e431b9
Source dataset
uspto-grants-2002_04
Patent number
US06372764B1

Reaction notes

Loading…