Dimethylformamide → (E)-tert-butyl 2-(3-(4-formylphenyl)acrylamido)-4-(thiophen-2-yl)phenylcarbamate

HRID 1907703Notes

Reaction equation

HRID 1907703 reaction equation
[CH:1]([C:3]1[CH:8]=[CH:7][C:6](/[CH:9]=[CH:10]/[C:11]([OH:13])=O)=[CH:5][CH:4]=1)=[O:2].S(Cl)(Cl)=O.CN(C)C=O.[NH2:23][C:24]1[CH:29]=[C:28]([C:30]2[S:31][CH:32]=[CH:33][CH:34]=2)[CH:27]=[CH:26][C:25]=1[NH:35][C:36](=[O:42])[O:37][C:38]([CH3:41])([CH3:40])[CH3:39]>ClCCCl.CN(C)C1C=CN=CC=1.O.C(Cl)Cl>[CH:1]([C:3]1[CH:4]=[CH:5][C:6](/[CH:9]=[CH:10]/[C:11]([NH:23][C:24]2[CH:29]=[C:28]([C:30]3[S:31][CH:32]=[CH:33][CH:34]=3)[CH:27]=[CH:26][C:25]=2[NH:35][C:36](=[O:42])[O:37][C:38]([CH3:40])([CH3:39])[CH3:41])=[O:13])=[CH:7][CH:8]=1)=[O:2]

Participants

9

Reactant 4

HCID 6228DimethylformamideHCID 24386Thionyl ChlorideHCID 5357280p-Formylcinnamic acidHCID 57717474tert-Butyl (2-amino-4-(thiophen-2-yl)phenyl)carbamate

Product 1

HCID 59737248(E)-tert-butyl 2-(3-(4-formylphenyl)acrylamido)-4-(thiophen-2-yl)phenylcarbamateYield 24.2%

Reagents, catalysts & solvents 4

HCID 142844-(Dimethylamino)pyridineCatalystHCID 111,2-DichloroethaneSolventHCID 962WaterSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
67 °C

Procedure

A suspension of (E)-3-(4-formylphenyl)acrylic acid 93 (1.046 g, 5.94 mmol) in 1,2-dichloroethane (30 mL) was treated with neat thionyl chloride (SOCl2) (0.9 mL, 12.3 mmol) and stirred at 67° C. then dimethyl formamide (0.3 mL) was slowly added; and the reaction mixture was allowed to stir at 67° C. for 30 min, cooled to room temperature, concentrated, diluted with dry benzene (40 mL) and concentrated again. The yellow residue was stored under vacuum for 3 h then suspended in pyridine (25 mL) and treated with amine 4 (1.113 g, 3.83 mmol) and 4-dimethylamino pyridine (DMAP) (156 mg). The suspension was stirred at room temperature for 3 days, diluted with H2O (10 mL) then stirred for additional 5 h. The solution was diluted with DCM, washed with 5% KHSO4, saturated NaHCO3, dried over MgSO4, filtered and concentrated to provide title compound 94 (0.415 g, 24% yield) after purification by flash chromatography (eluent: 30% to 50% AcOEt in hexanes). LRMS: 448.2 (calc) 471.0 (M+Na, obs)

Workup

  1. stirringto stir at 67° C. for 30 min
  2. temperaturecooled to room temperature
  3. concentrationconcentrated
  4. additiondiluted with dry benzene (40 mL)
  5. concentrationconcentrated again
  6. stirringThe suspension was stirred at room temperature for 3 days
  7. stirringthen stirred for additional 5 h
  8. washwashed with 5% KHSO4, saturated NaHCO3
  9. dry with materialdried over MgSO4
  10. filtrationfiltered
  11. concentrationconcentrated

Sources & evidence

ORD record
ord-fe6892c52ad744fb9df2ae22eb58b9d5
Source dataset
uspto-grants-2013_12
Patent number
US08598168B2

Reaction notes

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