Tributylamine → HCID 66938649, compound

HRID 1865573Notes

Reaction equation

HRID 1865573 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:13](=[O:21])[NH:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)=[C:6]([CH2:8][CH2:9][C:10]([OH:12])=[O:11])[CH:7]=1.I[C:23]1C=C(Cl)C=C[C:24]=1C(N)=O.C(OC(OCC)C=C)C.C(N(CCCC)CCCC)CCC>[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.CN(C=O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH2:23]([O:11][C:10](=[O:12])[CH2:9][CH2:8][C:6]1[CH:7]=[C:2]([Cl:1])[CH:3]=[CH:4][C:5]=1[C:13](=[O:21])[NH:14][C:15]1[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=1)[CH3:24]

Participants

8

Reactant 4

HCID 7622TributylamineHCID 624773,3-Diethoxy-1-propeneHCID 25192252HCID 25192252, compoundHCID 66938777HCID 66938777, compound

Product 1

HCID 66938649HCID 66938649, compoundYield 32%

Reagents, catalysts & solvents 3

HCID 74236Tetrabutylammonium BromideCatalystHCID 167845palladium(II) acetateCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

3-(5-Chloro-2-phenylcarbamoyl-phenyl)-propionic acid: A mixture of palladium acetate (0.022 g, 0.1 mmol), 2-iodo-4-chlorobenzamide (0.954 g, 2.67 mmol), 3,3-diethoxyprop-1-ene (0.693 g, 5.32 mmol), tetrabutylammonium bromide (0.86 g, 2.67 mmol), and tributylamine (0.984 g, 5.32 mmol) in DMF (25 mL) was heated at 80° C. overnight. The reaction was quenched with 1N HCl (50 mL) and stirred at rt for 1 h. The mixture was extracted with EtOAc and the combined organic layers were washed with 1N HCl, dried (MgSO4), filtered, and evaporated to give an oil. This residue was purified by flash chromatography to give 3-(5-chloro-2-phenylcarbamoyl-phenyl)-propionic acid ethyl ester (0.287 g, 32%). LC/MS m/z 332.3 (M+H)+. This intermediate (0.278 g, 0.865 mmol) was stirred with LiOH (21 mg, 0.865 mmol) in THF (10 mL) and water (0.5 mL) for 2 d. The mixture was diluted with water and washed with EtOAc. The aqueous layer was acidified with 1N HCl and extracted with EtOAc. The combined organic layers were dried (MgSO4), filtered, evaporated, and purified by reverse phase HPLC to give 183A. LC/MS m/z 304.3 (M+H)+. 1HNMR (CDCl3) δ 7.68 (d, J=8.0 Hz, 2H), 7.48 (d, J=8.2 Hz, 1H), 7.41-7.25 (m, H), 7.15 (t, 1H), 4.00 (bs, 1H), 3.11 (t, 2H), 2.80 (tm, 2H).

Workup

  1. customThe reaction was quenched with 1N HCl (50 mL)
  2. extractionThe mixture was extracted with EtOAc
  3. washthe combined organic layers were washed with 1N HCl
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. customevaporated
  7. customto give an oil
  8. customThis residue was purified by flash chromatography

Sources & evidence

ORD record
ord-e123114ca9c84180b46610de180e1d9a
Source dataset
uspto-grants-2009_12
Patent number
US07626039B2

Reaction notes

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