Tri-o-tolylphosphine → HCID 58641368, compound

HRID 1394913Notes

Reaction equation

HRID 1394913 reaction equation
[N:1]1([C:6]([O:8][C:9]([CH3:12])([CH3:11])[CH3:10])=[O:7])[CH2:5][CH:4]=[CH:3][CH2:2]1.Br[C:14]1[CH:19]=[C:18]([C:20]([F:23])([F:22])[F:21])[CH:17]=[CH:16][C:15]=1[F:24].C(N(CC)C(C)C)(C)C.C1(C)C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C>CN(C=O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C(=O)([O-])[O-].[Ag+2]>[F:24][C:15]1[CH:14]=[CH:19][C:18]([C:20]([F:21])([F:22])[F:23])=[CH:17][C:16]=1[CH:3]1[CH:4]=[CH:5][N:1]([C:6]([O:8][C:9]([CH3:12])([CH3:11])[CH3:10])=[O:7])[CH2:2]1

Participants

8

Reactant 4

HCID 80271Tri-o-tolylphosphineHCID 81531DiisopropylethylamineHCID 1442953-Bromo-4-fluorobenzotrifluorideHCID 5148195tert-Butyl 2,5-dihydro-1H-pyrrole-1-carboxylate

Product 1

HCID 58641368HCID 58641368, compound

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 178418647HCID 178418647, compoundCatalystHCID 6228DimethylformamideSolvent

Procedure

A deoxygenated solution of tert-butyl 2,5-dihydro-1H-pyrrole-1-carboxylate (3.38 g, 20.0 mmol, 10.0 equiv), 2-bromo-1-fluoro-4-(trifluoromethyl)benzene (486 mg, 2.00 mmol, 1 equiv), N,N-diisopropylethylamine (1.39 mL, 8.00 mmol, 4.00 equiv), tri-o-tolylphosphine (67 mg, 0.22 mmol, 0.11 equiv), palladium(II) acetate (22 mg, 0.10 mmol, 0.050 equiv), and silver carbonate (386 mg, 1.40 mmol, 0.700 equiv) in DMF (8.0 mL) was heated under nitrogen at 100° C. for 20 h. The reaction mixture was partitioned between saturated aqueous sodium bicarbonate solution (50 mL) and ethyl acetate (50 mL). The organic layer was washed with brine, dried over magnesium sulfate, and concentrated. The residue was purified by flash column chromatography (20% CH2Cl2 in hexanes, grading to 50% CH2Cl2 in hexanes) to give tert-butyl 3-[2-fluoro-5-(trifluoromethyl)phenyl]-2,3-dihydro-1H-pyrrole-1-carboxylate (3-1) as a colorless gum. 1H NMR (500 MHz, CDCl3) major rotamer: δ 7.51 (m, 2H), 7.15 (t, 1H, J=9.1 Hz), 6.74 (br s, 1H), 5.03 (br s, 1H), 4.48 (m, 1H), 4.17 (m, 1H), 3.61 (m, 1H), 1.50 (s, 9H).

Workup

  1. customThe reaction mixture was partitioned between saturated aqueous sodium bicarbonate solution (50 mL) and ethyl acetate (50 mL)
  2. washThe organic layer was washed with brine
  3. dry with materialdried over magnesium sulfate
  4. concentrationconcentrated
  5. customThe residue was purified by flash column chromatography (20% CH2Cl2 in hexanes, grading to 50% CH2Cl2 in hexanes)

Sources & evidence

ORD record
ord-8ab231a58e9c4e5faca9c4d0d3e8665b
Source dataset
uspto-grants-2008_03
Patent number
US07348440B2

Reaction notes

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