Ethyl Acetate → HCID 66925346, compound

HRID 1271376Notes

Reaction equation

HRID 1271376 reaction equation
[CH3:1][C:2]([O-:5])(C)[CH3:3].[Na+].P([C:16]([CH3:19])(C)C)(C(C)(C)C)C(C)(C)C.[N:20]1[CH:25]=[CH:24][CH:23]=[C:22]([CH2:26][NH:27][C:28]2[CH:33]=[CH:32][C:31](OC)=[C:30](OC3CCCC3)[CH:29]=2)[CH:21]=1.I[C:43]1[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=1.C[CH2:50][O:51]C(C)=O>C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH:2]1([O:5][C:22]2([CH2:26][N:27]([C:28]3[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=3)[C:43]3[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=3)[C:23]([O:51][CH3:50])=[CH:24][CH:25]=[N:20][CH2:21]2)[CH2:3][CH2:19][CH2:16][CH2:1]1

Participants

8

Reactant 5

HCID 8857Ethyl AcetateHCID 11575IodobenzeneHCID 83681Tris(1,1-dimethylethyl)phosphineHCID 12992942HCID 12992942, compoundHCID 23676156Sodium t-butoxide

Product 1

HCID 66925346HCID 66925346, compound

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent2×

Procedure

To a 100 mL oven dried, argon flushed flask was added in the following order 0.59 g (6.10 mmol) of NaOtBu, 360 mg of Pd2dba3, 20 mL of toluene, 0.14 mL of P(tBu)3, and a 20 mL solution of 1.3 g (4.36 mmol) of N-(3-pyridylmethyl)-3-cyclopentyloxy-4-methoxyaniline in toluene. With stirring, 3.1 g (15 mmol) of iodobenzene was added dropwise and the mixture was stirred for 18 hours. The reaction mixture was diluted with EtOAc and washed twice with H2O and extracted with 3×15 mL of 3N HCl. The combined acid extracts were washed with 15 mL of EtOAc and then carefully neutralized with 6N NaOH to pH greater than 12. The basic solution was extracted with 2×15 mL of EtOAc and the combined organic fractions were subsequently washed with 15 mL of H2O and brine, dried (MgSO4), and concentrated. The residue was purified by chromatography over silica gel (Biotage Flash 40M) eluting with 25% EtOAc in hexanes. The material was further purified by crystallization from hexanes to give 550 mg of a white solid. 1H NMR (CDCl3) δ 8.61 (s, 1H), 8.49 (d, 1H, J=4.2 Hz), 7.67 (d, 1H, 7.9 Hz), 7.30–7.10 (m, 3H), 6.90–6.80 (m, 4H), 6.80–6.60 (m, 2H), 4.94 (s, 2H), 4.64 (p, 1H, J=4.1 Hz), 3.84 (s, 3H), 1.86–1.70 (m, 6H), 1.65–1.45 (m, 2H).

Workup

  1. customTo a 100 mL oven dried
  2. stirringthe mixture was stirred for 18 hours
  3. washwashed twice with H2O
  4. extractionextracted with 3×15 mL of 3N HCl
  5. washThe combined acid extracts were washed with 15 mL of EtOAc
  6. extractionThe basic solution was extracted with 2×15 mL of EtOAc
  7. washthe combined organic fractions were subsequently washed with 15 mL of H2O and brine
  8. dry with materialdried (MgSO4)
  9. concentrationconcentrated
  10. customThe residue was purified by chromatography over silica gel (Biotage Flash 40M)
  11. washeluting with 25% EtOAc in hexanes
  12. customThe material was further purified by crystallization from hexanes

Sources & evidence

ORD record
ord-39696eef30a644b8b7914b0173b67242
Source dataset
uspto-grants-2007_04
Patent number
US07205320B2

Reaction notes

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