Diisopropylethylamine → (S)-tert-butyl 3-(benzyloxycarbonylamino)-2-oxo-1,4'-bipiperidine-1'-carboxylate

HRID 407926Notes

Reaction equation

[CH2:1]([O:8][C:9]([NH:11][C@@H:12]([CH2:16][CH2:17][CH2:18][NH:19][CH:20]1[CH2:25][CH2:24][N:23]([C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[CH2:22][CH2:21]1)[C:13](O)=[O:14])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl.C(N=C=NCCCN(C)C)C.C(N(C(C)C)C(C)C)C>CN(C=O)C>[CH2:1]([O:8][C:9]([NH:11][C@H:12]1[CH2:16][CH2:17][CH2:18][N:19]([CH:20]2[CH2:21][CH2:22][N:23]([C:26]([O:28][C:29]([CH3:31])([CH3:32])[CH3:30])=[O:27])[CH2:24][CH2:25]2)[C:13]1=[O:14])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

Conditions

Temperature: 0 °C

Procedure

Crude (S)-2-(benzyloxycarbonylamino)-5-(1-(tert-butoxycarbonyl)piperidin-4-ylamino)pentanoic acid (84 g, 187 mmol) was dissolved in DMF (600 mL), and cooled to 0° C. N1-((ethylimino)methylene)-N3,N3-dimethylpropane-1,3-diamine hydrochloride (35.8 g, 187 mmol) and N-ethyl-N-isopropylpropan-2-amine (32.5 mL, 187 mmol) were added and the reaction stirred at ambient temperature overnight. The reaction was concentrated and dissolved in EtOAc (1000 mL), washed with 1N HCl, saturated aqueous NaHCO3 and brine, dried over Na2SO4, filtered and concentrated. The residue was purified over silica gel (50% EtOAc in hexanes) to afford (S)-tert-butyl 3-(benzyloxycarbonylamino)-2-oxo-1,4′-bipiperidine-1′-carboxylate (49 g, 114 mmol, 60.8% yield) as white solid.

Workup

concentrationThe reaction was concentrated
dissolutiondissolved in EtOAc (1000 mL)
washwashed with 1N HCl, saturated aqueous NaHCO3 and brine
dry with materialdried over Na2SO4
filtrationfiltered
concentrationconcentrated
customThe residue was purified over silica gel (50% EtOAc in hexanes)

Sources & evidence

ORD record: ord-9c135f3c0e2a4a55ade167de8f0ee53e
Source dataset: uspto-grants-2014_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08754226B2

Reaction notes

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