Triethylamine → 2-(trimethylsilyl)ethyl (1S,2R,3S,5S)-2-(1,3-dioxoisoindolin-2-yl)bicyclo[3.1.0]hexan-3-ylcarbamate

HRID 56409Notes

Reaction equation

HRID 56409 reaction equation
[NH2:1][C@H:2]1[CH2:7][C@H:6]2[C@H:4]([CH2:5]2)[C@H:3]1[N:8]1[C:16](=[O:17])[C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[C:9]1=[O:18].[C:19](=O)([O:28][CH2:29][CH2:30][Si:31]([CH3:34])([CH3:33])[CH3:32])[O:20]N1C(=O)CCC1=O.C(N(CC)CC)C>O1CCOCC1.O.C(OCC)(=O)C>[O:18]=[C:9]1[C:10]2[C:15](=[CH:14][CH:13]=[CH:12][CH:11]=2)[C:16](=[O:17])[N:8]1[C@H:3]1[C@@H:2]([NH:1][C:19](=[O:20])[O:28][CH2:29][CH2:30][Si:31]([CH3:34])([CH3:33])[CH3:32])[CH2:7][C@H:6]2[C@@H:4]1[CH2:5]2

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 50183862,5-Dioxopyrrolidin-1-yl 2-(trimethylsilyl)ethyl carbonateHCID 1180362842-((1S,2R,3S,5S)-3-aminobicyclo[3.1.0]hexan-2-yl)isoindoline-1,3-dione

Product 1

HCID 1317369252-(trimethylsilyl)ethyl (1S,2R,3S,5S)-2-(1,3-dioxoisoindolin-2-yl)bicyclo[3.1.0]hexan-3-ylcarbamateYield 78.3%

Reagents, catalysts & solvents 2

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

Procedure

A solution of 2-((1S,2R,3S,5S)-3-aminobicyclo[3.1.0]hexan-2-yl)isoindoline-1,3-dione (2.0 g, 8.264 mmol), 2,5-dioxopyrrolidin-1-yl 2-(trimethylsilyl)ethyl carbonate (3.2 g, 12.396 mmol) and triethylamine (3.4 mL, 24.792 mmol) in dioxane/water (100 mL, v/v=1/1) was stirred at room temperature for 1.5 hours. The reaction mixture was then diluted with ethyl acetate (100 mL), washed by 1 M hydrochloric acid (2×50 mL), saturated sodium bicarbonate solution (2×50 mL) and brine (50 mL). The organic layer was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (ethyl acetate:petroleum ether=1:4) to afford the title compound (2.5 g, 78%) as a yellow oil. MS (ES+) C20H26N2O4Si requires: 386, found: 410 [M+23]+.

Workup

  1. washwashed by 1 M hydrochloric acid (2×50 mL), saturated sodium bicarbonate solution (2×50 mL) and brine (50 mL)
  2. concentrationThe organic layer was concentrated under reduced pressure
  3. customthe residue was purified by silica gel column chromatography (ethyl acetate:petroleum ether=1:4)

Sources & evidence

ORD record
ord-d568af3d021248bf84b09bb6603c0d1f
Source dataset
uspto-grants-2016_09
Patent number
US09434700B2

Reaction notes

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