N-Allylaniline → (S)-tert-butyl 1-(allyl(phenyl)amino)-1-oxopent-4-en-2-ylcarbamate

HRID 529519Notes

Reaction equation

HRID 529519 reaction equation
[C:1]([O:5][C:6]([NH:8][C@@H:9]([CH2:13][CH:14]=[CH2:15])[C:10]([OH:12])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH2:16]([NH:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)[CH:17]=[CH2:18].CCN(C(C)C)C(C)C>CCOC(C)=O>[CH2:16]([N:19]([C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)[C:10](=[O:12])[C@@H:9]([NH:8][C:6](=[O:7])[O:5][C:1]([CH3:2])([CH3:3])[CH3:4])[CH2:13][CH:14]=[CH2:15])[CH:17]=[CH2:18]

Participants

5

Reactant 3

HCID 68525N-AllylanilineHCID 81531DiisopropylethylamineHCID 2734487(2S)-2-(((tert-butoxy)carbonyl)amino)pent-4-enoic acid

Product 1

HCID 68311024(S)-tert-butyl 1-(allyl(phenyl)amino)-1-oxopent-4-en-2-ylcarbamateYield 55.2%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent2×

Conditions

Temperature
0 °C

Procedure

A solution of N-propylphosphonic acid anhydride cyclic trimer (50% reagent in EtOAc solution, 1.26 mL, 2.14 mmol) was added to a degassed solution of (S)-2-(tert-butoxycarbonylamino)pent-4-enoic acid (230 mg, 1.07 mmol), N-allylaniline (142 mg, 1.07 mmol), and Hunig's Base (0.560 mL, 3.21 mmol) at 0° C. The reaction mixture was stirred under argon for 2 min at 0° C. and then warmed to rt and stirred for 1 hr. The reaction mixture was diluted with EtOAc, washed with saturated aqueous NaHCO3 and saturated aqueous NaCl, dried over Na2SO4, filtered and concentrated. The crude product was purified using silica gel chromatography (ISCO system) eluting with a gradient of 0-30% EtOAc/Hex to give (S)-tert-butyl 1-(allyl(phenyl)amino)-1-oxopent-4-en-2-ylcarbamate (195 mg, 0.590 mmol, 55.2% yield) as a colorless oil. 1H NMR (400 MHz, CDCl3) δ ppm 7.43 (t, J=7.4 Hz, 2H), 7.36 (t, J=7.3 Hz, 1H), 7.24 (d, J=7.5 Hz, 2H), 5.91-5.78 (m, 1H), 5.63-5.49 (m, 1H), 5.23 (d, J=8.4 Hz, 1H), 5.18-5.05 (m, 2H), 5.05-4.94 (m, 2H), 4.43-4.19 (m, 3H), 2.33-2.23 (m, 1H), 2.20-2.08 (m, 1H), 1.45 (s, 9H).

Workup

  1. temperaturewarmed to rt
  2. stirringstirred for 1 hr
  3. washwashed with saturated aqueous NaHCO3 and saturated aqueous NaCl
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude product was purified
  8. washeluting with a gradient of 0-30% EtOAc/Hex

Sources & evidence

ORD record
ord-c9e95d5242de4f528ec464ddcde00f3d
Source dataset
uspto-grants-2016_05
Patent number
US09346852B2

Reaction notes

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