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

HRID 69912Notes

Reaction equation

HRID 69912 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

5

Reactant 4

HCID 6386tert-ButanolHCID 81531DiisopropylethylamineHCID 199401P,P-Diphenylphosphinic azideHCID 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.

Workup

  1. customThe solvent was removed under reduced pressure
  2. additionTo the crude was added EtOAc (300 mL)
  3. washthe organic layer was washed with saturated NaHCO3 (150 mL) and brine
  4. customdried
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customto give the crude
  8. customThe crude material was further purified by silica gel chromatography

Sources & evidence

ORD record
ord-7977253b7eaf4da18275906227078f2e
Source dataset
uspto-grants-2014_09
Patent number
US08822497B2

Reaction notes

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