1,2-Dichloroethane → (S)-tert-butyl 1-(benzyl(but-3-enyl)amino)-1-oxopent-4-en-2-ylcarbamate

HRID 529507Notes

Reaction equation

HRID 529507 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:23][CH2:24][CH2:25][CH:26]=[CH2:27])[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1>CN(C=O)C.CCOC(C)=O>[CH2:16]([N:23]([CH2:24][CH2:25][CH:26]=[CH2:27])[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])[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1

Participants

7

Reactant 4

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 2734487(2S)-2-(((tert-butoxy)carbonyl)amino)pent-4-enoic acidHCID 4366091N-Benzylbut-3-en-1-amine

Product 1

HCID 68311224(S)-tert-butyl 1-(benzyl(but-3-enyl)amino)-1-oxopent-4-en-2-ylcarbamateYield 40.5%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of (S)-2-(tert-butoxycarbonylamino)pent-4-enoic acid (400 mg, 1.86 mmol), N-benzylbut-3-en-1-amine (449 mg, 2.79 mmol) in DMF (5 mL) was added EDC (410 mg, 2.14 mmol), HOBt (370 mg, 2.42 mmol) and followed by TEA (0.259 mL, 1.858 mmol). The reaction was stirred at rt for 3 days. The reaction was diluted with EtOAc and washed with water (2×), 1 M aqueous KHSO4 (2×), saturated aqueous NaHCO3 (2×) and saturated aqueous NaCl. The organic layer was separated, dried over Na2SO4, filtered and concentrated. The crude product was purified using silica gel chromatography (ISCO system) eluting with a gradient of 0-60% EtOAc/Hex to give (S)-tert-butyl 1-(benzyl(but-3-enyl)amino)-1-oxopent-4-en-2-ylcarbamate (270 mg, 0.753 mmol, 40.5% yield). Anal. Calcd. for C21H30N2O3 m/z 358.4. found: 359.1 (M+H)+; 1H NMR (400 MHz, CDCl3) δ ppm 7.43-7.13 (m, 5H), 5.85-5.62 (m, 2H), 5.40-5.27 (m, 1H), 5.19-4.97 (m, 3H), 4.87 and 4.37 (d, J=14.9 Hz, 1H), 4.76-4.51 (m, 2H), 3.59-3.22 (m, 3H), 2.39 (ddq, J=25.6, 21.3, 7.1 Hz, 4H), 1.44 and 1.42 (s, 9H).

Workup

  1. washwashed with water (2×), 1 M aqueous KHSO4 (2×), saturated aqueous NaHCO3 (2×) and saturated aqueous NaCl
  2. customThe organic layer was separated
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude product was purified
  7. washeluting with a gradient of 0-60% EtOAc/Hex

Sources & evidence

ORD record
ord-0783fced73ec4f928c9d67ed1fbaa113
Source dataset
uspto-grants-2016_05
Patent number
US09346852B2

Reaction notes

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