Triethylamine → Trans-Ethyl-7-{[3-(3-Hydroxy-phenyl)-allyl]-methanesulfonyl-amino}-heptanoate

HRID 890724Notes

Reaction equation

HRID 890724 reaction equation
[CH2:1]([O:3][C:4](=[O:19])[CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][N:11]([CH2:16][CH:17]=[CH2:18])[S:12]([CH3:15])(=[O:14])=[O:13])[CH3:2].C([O:23][C:24]1[CH:29]=[CH:28][CH:27]=[C:26](I)[CH:25]=1)(=O)C.C(N(CC)CC)C.S([O-])([O-])(=O)=S.[Na+].[Na+]>CN(C=O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C(Cl)Cl>[CH2:1]([O:3][C:4](=[O:19])[CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][N:11]([CH2:16]/[CH:17]=[CH:18]/[C:26]1[CH:27]=[CH:28][CH:29]=[C:24]([OH:23])[CH:25]=1)[S:12]([CH3:15])(=[O:13])=[O:14])[CH3:2]

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 24477Sodium ThiosulfateHCID 131017693-Iodophenyl acetateHCID 542860497-(Allyl-methanesulfonyl-amino)-heptanoic acid ethyl ester

Product 1

HCID 22246921Trans-Ethyl-7-{[3-(3-Hydroxy-phenyl)-allyl]-methanesulfonyl-amino}-heptanoateYield 28.8%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of 7-(allyl-methanesulfonyl-amino)-heptanoic acid ethyl ester (250 mg, 0.86 mmol), 1-acetyloxy-3-iodo-benzene (225 mg, 0.86 mmol), and triethylamine (139 mL, 1 mmol) in DMF (3 mL) was added palladium acetate (25 mg). The reaction was heated to 80° C. under nitrogen for 24 h. The mixture was cooled to room temperature and aqueous sodium thiosulfate and CH2Cl2 were added. The aqueous solution was extracted with CH2Cl2 (2×) and the combined organic layers were washed with water (1×) and brine (1×). The organic solution was dried with MgSO4, filtered, and concentrated in vacuo. The product was purified by radial chromatography (hexanes to 25% EtOAc/hexanes) to afford the title compound of Step A (95 mg). 1H NMR (CDCl3 400 MHz) δ 6.88–7.34 (m, 4H), 6.53–6.60 (m, 1H), 6.13–6.20 (m, 1H), 4.10 (q, 2H), 3.95 (d, 2H), 3.17–3.21 (m, 2H), 2.85 (s, 3H), 2.24–2.31 (m, 2H), 2.31 (s, 3H), 1.56–1.62 (m, 4H), 1.27–1.33 (m, 4H), 1.23 (t, 3H).

Workup

  1. temperatureThe mixture was cooled to room temperature
  2. extractionThe aqueous solution was extracted with CH2Cl2 (2×)
  3. washthe combined organic layers were washed with water (1×) and brine (1×)
  4. dry with materialThe organic solution was dried with MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe product was purified by radial chromatography (hexanes to 25% EtOAc/hexanes)

Sources & evidence

ORD record
ord-3a501798220946c0b6d6df18b58ff785
Source dataset
uspto-grants-2006_02
Patent number
US06998423B2

Reaction notes

Loading…