Triethylamine → cis-Tert-butyl 4-(benzyloxycarbonylamino)-3-((2-(trimethylsilyl)ethoxy)-carbonylamino)piperidine-1-carboxylate

HRID 56419Notes

Reaction equation

HRID 56419 reaction equation
[NH2:1][C@H:2]1[C@@H:7]([NH:8][C:9]([O:11][CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=[O:10])[CH2:6][CH2:5][N:4]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:3]1.[C:26](=O)([O:35][CH2:36][CH2:37][Si:38]([CH3:41])([CH3:40])[CH3:39])[O:27]N1C(=O)CCC1=O.C(N(CC)CC)C>O1CCOCC1.O.C(OCC)(=O)C>[CH2:12]([O:11][C:9]([NH:8][C@H:7]1[CH2:6][CH2:5][N:4]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:3][C@H:2]1[NH:1][C:26]([O:35][CH2:36][CH2:37][Si:38]([CH3:41])([CH3:40])[CH3:39])=[O:27])=[O:10])[C:13]1[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=1

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 50183862,5-Dioxopyrrolidin-1-yl 2-(trimethylsilyl)ethyl carbonateHCID 69440349tert-Butyl (3R,4S)-3-amino-4-{[(benzyloxy)carbonyl]amino}piperidine-1-carboxylate

Product 1

HCID 131736928cis-Tert-butyl 4-(benzyloxycarbonylamino)-3-((2-(trimethylsilyl)ethoxy)-carbonylamino)piperidine-1-carboxylateYield 83%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 218864351,4-Dioxane--water (1/1)Solvent

Procedure

A solution of cis-tert-butyl 3-amino-4-(benzyloxycarbonylamino)piperidine-1-carboxylate (3.0 g, 8.6 mmol), 2,5-dioxopyrrolidin-1-yl 2-(trimethylsilyl)ethyl carbonate (2.5 g, 9.5 mmol) and triethylamine in dioxane/water (40 mL, v/v=1/1) was stirred at room temperature for 4 hours. After that, the solution was diluted with ethyl acetate (200 mL), and washed by 1 M hydrochloric acid (50 mL), saturated sodium bicarbonate solution (50 mL) and brine (50 mL). The organic layer was dried over sodium sulfate, filtered and concentrated. The residue was purified by silica gel column chromatography (petroleum ether/ethyl acetate=4/1) to afford the title compound (3.5 g, 83%) as a white solid. MS (ES+) C24H39N3O6Si requires: 493, found: 516 [M+23]+.

Workup

  1. washwashed by 1 M hydrochloric acid (50 mL), saturated sodium bicarbonate solution (50 mL) and brine (50 mL)
  2. dry with materialThe organic layer was dried over sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe residue was purified by silica gel column chromatography (petroleum ether/ethyl acetate=4/1)

Sources & evidence

ORD record
ord-b8ec96f4c4c14f89bb882e672bc12439
Source dataset
uspto-grants-2016_09
Patent number
US09434700B2

Reaction notes

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