Triphenylphosphine → tert-Butyl (3R)-3-[2-(trifluoromethyl)phenoxy]pyrrolidine-1-carboxylate

HRID 2355052Notes

Reaction equation

HRID 2355052 reaction equation
[OH:1][C@@H:2]1[CH2:6][CH2:5][N:4]([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[CH2:3]1.[F:14][C:15]([F:24])([F:23])[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=1O.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CCOC(/N=N/C(OCC)=O)=O>C1COCC1>[F:14][C:15]([F:24])([F:23])[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=1[O:1][C@@H:2]1[CH2:6][CH2:5][N:4]([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[CH2:3]1

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 679582-TrifluoromethylphenolHCID 5462977Diethyl azodicarboxylateHCID 6544479tert-Butyl (3R)-3-hydroxypyrrolidine-1-carboxylate

Product 1

HCID 57356986tert-Butyl (3R)-3-[2-(trifluoromethyl)phenoxy]pyrrolidine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of tert-butyl (3R)-3-hydroxypyrrolidine-1-carboxylate (5 g, 26.7 mmol), 2-(trifluoromethyl)phenol (4.8 h, 29.4 mmol) and triphenylphosphine (8.4 g, 32 mmol) in THF (75 mL) at rt was added DEAD (5.1 mL, 32 mmol) over 5-10 min. The mixture was stirred at rt for 2 days. Solvent was evaporated. The residue was diluted with EtOAc and washed successively with 1 N aqueous NaOH and brine. The EtOAc layer was separated, dried (Na2SO4) and concentrated. Chromatography over silica gel and elution with hexanes/EtOAc (10:1, then 3:1) gave tert-butyl (3R)-3-[2-(trifluoromethyl)phenoxy]pyrrolidine-1-carboxylate as a colorless oil, which solidified on standing. 1H NMR (500 MHz, acetone-d6): δ 7.63 (m, 2 H), 7.31 (d, 1 H), 7.13 (t, 1 H), 5.26 (s, 1 H), 3.68-3.43 (m, 4 H), 2.21 (m, 2 H), 1.45 (s, 9 H).

Workup

  1. customSolvent was evaporated
  2. additionThe residue was diluted with EtOAc
  3. washwashed successively with 1 N aqueous NaOH and brine
  4. customThe EtOAc layer was separated
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated
  7. washChromatography over silica gel and elution with hexanes/EtOAc (10:1

Sources & evidence

ORD record
ord-4b5ad053c947417da88435b31069672c
Source dataset
uspto-grants-2010_07
Patent number
US07754745B2

Reaction notes

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