1,2-Dichloroethane → tert-butyl (S)-1-oxo-1-((R)-2-vinylpiperidin-1-yl)pent-4-en-2-ylcarbamate

HRID 529525Notes

Reaction equation

HRID 529525 reaction equation
CCN(C(C)C)C(C)C.[C:10]([O:14][C:15]([NH:17][C@@H:18]([CH2:22][CH:23]=[CH2:24])[C:19]([OH:21])=O)=[O:16])([CH3:13])([CH3:12])[CH3:11].Cl.[CH:26]([C@H:28]1[CH2:33][CH2:32][CH2:31][CH2:30][NH:29]1)=[CH2:27].C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1>C(Cl)Cl>[O:21]=[C:19]([N:29]1[CH2:30][CH2:31][CH2:32][CH2:33][C@@H:28]1[CH:26]=[CH2:27])[C@@H:18]([NH:17][C:15](=[O:16])[O:14][C:10]([CH3:11])([CH3:12])[CH3:13])[CH2:22][CH:23]=[CH2:24]

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 2734487(2S)-2-(((tert-butoxy)carbonyl)amino)pent-4-enoic acidHCID 50941258(R)-2-vinylpiperidine hydrochloride

Product 1

HCID 68309883tert-butyl (S)-1-oxo-1-((R)-2-vinylpiperidin-1-yl)pent-4-en-2-ylcarbamateYield 69.8%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

DIPEA (1.801 gm, 13.94 mmol) was slowly added to a 0° C. mixture of (S)-2-(tert-butoxycarbonylamino)pent-4-enoic acid (1.00 gm, 4.65 mmol), (R)-2-vinylpiperidine hydrochloride (0.720 gm, 4.88 mol), EDC (1.02 gm, 5.34 mmol) and HOBt (0.818 gm, 5.34 mmol) in DCM (19 mL). The yellow reaction mixture was then stirred at rt for 3 days. The reaction mixture was concentrated to remove the DCM and the residue was partitioned between EtOAc and 0.5 N aqueous HCl. The organic phase was isolated, washed with saturated aqueous NaHCO3 and saturated aqueous NaCl, dried over MgSO4, filtered and concentrated. The crude product was purified using silica gel chromatography (ISCO system) eluting with a gradient of 0-100% EtOAc/Hex to give tert-butyl (S)-1-oxo-1-((R)-2-vinylpiperidin-1-yl)pent-4-en-2-ylcarbamate (1.00 gm, 3.24 mmol, 69.8% yield) as a colorless oil. Anal. Calcd. for C17H28N2O3 m/z 308.3. found: 309.0 (M+H)+.

Workup

  1. concentrationThe reaction mixture was concentrated
  2. customto remove the DCM
  3. customthe residue was partitioned between EtOAc and 0.5 N aqueous HCl
  4. customThe organic phase was isolated
  5. washwashed with saturated aqueous NaHCO3 and saturated aqueous NaCl
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe crude product was purified
  10. washeluting with a gradient of 0-100% EtOAc/Hex

Sources & evidence

ORD record
ord-c12771cd27f54f46b441a6c6e5d7af81
Source dataset
uspto-grants-2016_05
Patent number
US09346852B2

Reaction notes

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