Diisopropylethylamine → (E)-tert-Butyl 2-(2-bromo-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)benzamido)ethylcarbamate

HRID 1502923Notes

Reaction equation

HRID 1502923 reaction equation
C1CN([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.[Br:43][C:44]1[CH:52]=[C:51](/[CH:53]=[CH:54]/[CH:55]([C:60]2[CH:65]=[C:64]([Cl:66])[C:63]([Cl:67])=[C:62]([Cl:68])[CH:61]=2)[C:56]([F:59])([F:58])[F:57])[CH:50]=[CH:49][C:45]=1[C:46](O)=[O:47].[NH2:69][CH2:70][CH2:71][NH:72][C:73](=[O:79])[O:74][C:75]([CH3:78])([CH3:77])[CH3:76]>C(Cl)Cl.O>[Br:43][C:44]1[CH:52]=[C:51](/[CH:53]=[CH:54]/[CH:55]([C:60]2[CH:61]=[C:62]([Cl:68])[C:63]([Cl:67])=[C:64]([Cl:66])[CH:65]=2)[C:56]([F:59])([F:58])[F:57])[CH:50]=[CH:49][C:45]=1[C:46]([NH:69][CH2:70][CH2:71][NH:72][C:73](=[O:79])[O:74][C:75]([CH3:76])([CH3:78])[CH3:77])=[O:47]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 187201N-BOC-ethylenediamineHCID 2724699PyBOPHCID 86722549(E)-2-bromo-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)benzoic acid

Product 1

HCID 86722550(E)-tert-Butyl 2-(2-bromo-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)benzamido)ethylcarbamateYield 39%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

PyBOP (420 mg, 0.82 mmol) and DIPEA (0.410 mL, 2.46 mmol) were added to a stirred solution of (E)-2-bromo-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)benzoic acid (400 mg, 0.82 mmol) and tert-butyl 2-aminoethylcarbamate (130 mg, 0.82 mmol) in CH2Cl2 (10 mL) and the reaction mixture was stirred at ambient temperature for 18 h. Water was added to the reaction mixture and extracted with CH2Cl2 (25 mL). The organic layer was washed with 2N HCl followed by saturated NaHCO3 and brine. The organic layer was dried (Na2SO4), filtered, concentrated and the residue was purified by column chromatography on silica (100-200 mesh) eluting with 40% EtOAc in petroleum ether to afford the title compound as a brown solid (200 mg, 39%): 1H NMR (400 MHz, DMSO-d6) δ 8.38 (t, J=5.2 Hz, 1H), 7.91-7.89 (m, 3H), 7.58 (d, J=6.8 Hz, 1H), 7.41 (d, J=7.6 Hz, 1H), 6.99 (dd, J=15.6, 9.2 Hz, 1H), 6.84 (t, J=6.0 Hz, 1H), 6.76 (t, J=15.6 Hz, 1H), 4.84-4.80 (m, 1H), 3.24-3.20 (m, 2H), 3.11-3.08 (m, 2H), 1.30 (s, 9H); ESIMS m/z 628.80 ([M+H]+); IR (thin film) 3365, 1701, 1167, 699, 555 cm−1.

Workup

  1. extractionextracted with CH2Cl2 (25 mL)
  2. washThe organic layer was washed with 2N HCl
  3. dry with materialThe organic layer was dried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customthe residue was purified by column chromatography on silica (100-200 mesh)
  7. washeluting with 40% EtOAc in petroleum ether

Sources & evidence

ORD record
ord-4c7027730fa44dca9bf813960a18bc06
Source dataset
uspto-grants-2015_12
Patent number
US09211280B2

Reaction notes

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