4-Fluoroiodobenzene → HCID 15342619, compound

HRID 1166298Notes

Reaction equation

HRID 1166298 reaction equation
[CH2:1]([O:3][C:4](=[O:36])[CH:5]([N:22]=[C:23]([C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)[CH2:6][C:7]1[CH:12]=[CH:11][C:10](B2OC(C)(C)C(C)(C)O2)=[CH:9][CH:8]=1)[CH3:2].[F:37][C:38]1[CH:43]=[CH:42][C:41](I)=[CH:40][CH:39]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].COCCOC>[CH2:1]([O:3][C:4](=[O:36])[CH:5]([N:22]=[C:23]([C:30]1[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=1)[C:24]1[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=1)[CH2:6][C:7]1[CH:12]=[CH:11][C:10]([C:41]2[CH:42]=[CH:43][C:38]([F:37])=[CH:39][CH:40]=2)=[CH:9][CH:8]=1)[CH3:2]

Participants

6

Reactant 3

HCID 96054-FluoroiodobenzeneHCID 62657Potassium Phosphate, TribasicHCID 11730571HCID 11730571, compound

Product 1

HCID 15342619HCID 15342619, compound

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 80711,2-DimethoxyethaneSolvent

Procedure

2-(Benzhydrylidene-amino)-3-(4′-fluoro-biphenyl-4-yl)-propionic acid ethyl ester is prepared according to the general procedure reported by Satoh et al. (Tetrahedron Letter Vol. 48, 7645 (1997)). A 50-mL flask is charged with the boronate intermediate of step 1 (600 mg, 1.01 mmol), 1-fluoro-4-iodo-benzene (247 mg, 1.11 mmol), PdCl2(dppf) (37 mg, 0.051 mmol), K3PO4 (860 mg, 4.04 mmol), and 10 mL of DME. The reaction mixture is heated at reflux for 12 hours then cooled to room temperature, and partitioned between EtOAc and water. The organic phase is separated and washed with brine, dried over MgSO4, filtered, and concentrated. The residue is purified by chromatography on silica gel (gradient elution with 5-10% EtOAc/hexane) to furnish the above imine as a light brown oil. 1H NMR (300 MHz, CDCl3) δ 7.50-7.70 (m, 4H), 7.25-7.40 (m, 8H), 7.05-7.20 (m, 4H), 6.55-6.70 (m, 2H), 4.15-4.30 (m, 3H), 3.15-3.35 (m, 2H), 1.15-1.25 (two t, 3H).

Workup

  1. temperatureThe reaction mixture is heated
  2. temperatureat reflux for 12 hours
  3. custompartitioned between EtOAc and water
  4. customThe organic phase is separated
  5. washwashed with brine
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue is purified by chromatography on silica gel (gradient elution with 5-10% EtOAc/hexane)

Sources & evidence

ORD record
ord-e96fb0d4ecf14140a917e573cc9f425a
Source dataset
uspto-grants-2003_09
Patent number
US06613782B2

Reaction notes

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