tert-Butanol → cis-(+/-)-Benzyl 3,5-bis(tert-butoxycarbonylamino)piperidine-1-carboxylate

Reaction equation

[CH2:1]([O:8][C:9]([N:11]1[CH2:16][C@H:15]([NH:17][C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:14][C@H:13](C(O)=O)[CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C1C=CC(P(N=[N+]=[N-])(C2C=CC=CC=2)=[O:35])=CC=1.CC[N:47]([CH:51](C)C)C(C)C.[CH3:54][C:55]([OH:58])([CH3:57])[CH3:56]>>[C:55]([O:58][C:51]([NH:47][C@H:13]1[CH2:14][C@@H:15]([NH:17][C:18]([O:20][C:21]([CH3:23])([CH3:22])[CH3:24])=[O:19])[CH2:16][N:11]([C:9]([O:8][CH2:1][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)=[O:10])[CH2:12]1)=[O:35])([CH3:57])([CH3:56])[CH3:54]

Participants

Reactant 4

HCID 6386tert-Butanol

HCID 81531Diisopropylethylamine

HCID 199401P,P-Diphenylphosphinic azide

HCID 86656441HCID 86656441, compound

Product 1

HCID 58865133cis-(+/-)-Benzyl 3,5-bis(tert-butoxycarbonylamino)piperidine-1-carboxylateYield 23%

Procedure

To a solution of cis-(+/−)-1-(benzyloxycarbonyl)-5-(tert-butoxycarbonylamino) piperidine-3-carboxylic acid (1.2 g, 3.17 mmol), DPPA (Diphenylphosphoryl azide, 1.04 g, 3.81 mmol) and DIEA (1.1 mL, 6.35 mmol) in t-BuOH (10 mL) was heated to 90° C. over night. The solvent was removed under reduced pressure. To the crude was added EtOAc (300 mL), the organic layer was washed with saturated NaHCO3 (150 mL) and brine, dried and filtered, and concentrated to give the crude. The crude material was further purified by silica gel chromatography to yielding cis-(+/−)-benzyl 3,5-bis(tert-butoxycarbonylamino)piperidine-1-carboxylate, (23%). LCMS (m/z): 350(minus one Boc(MH+); LC Rt=4.40 min.