Reaktion #157172

ord-1677d6cbeadb4e1eb2c04576732108f0

Reaktionsgleichung

CC(C)(C)OC(=O)N[C@H]1C[C@@H](CO)CN(C(=O)OCc2ccccc2)C1
cis (+/−)-benzyl 3-(tert-butoxycarbonylamino)-5-(hydroxymethyl)piperidine-1-carboxylate
O=S(=O)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)F
perfluorobutanesulfonylfluoride
CCN(CC)CC
triethylamine
CCN(CC)CC
triethylamine
→
CC(C)(C)OC(=O)N[C@H]1C[C@@H](CF)CN(C(=O)OCc2ccccc2)C1
cis (+/−)-benzyl 3-(tert-butoxycarbonylamino)-5-(fluoromethyl)piperidine-1-carboxylate
Ausbeute 45.0%

Edukte

CC(C)(C)OC(=O)N[C@H]1C[C@@H](CO)CN(C(=O)OCc2ccccc2)C1
cis (+/−)-benzyl 3-(tert-butoxycarbonylamino)-5-(hydroxymethyl)piperidine-1-carboxylate
O=S(=O)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)F
perfluorobutanesulfonylfluoride
CCN(CC)CC
triethylamine
CCN(CC)CC
triethylamine

Reagenzien

Keine

Lösungsmittel

C1CCOC1
tetrahydrofuran

Reaktionsbedingungen

Detaillierte Bedingungen
See reaction.notes.procedure_details.

Aufarbeitung

  1. 1
    WaschenUpon dilution with ethyl acetate (50×) the solution was washed with 1N HCl, NaHCO3(sat.) and brine
  2. 2
    Trocknenwas dried over MgSO4
  3. 3
    Filtrationfiltered
  4. 4
    Einengenconcentrated
  5. 5
    Sonstigepurified by column chromatography (25-40% ethyl acetate/hexanes)

Vorschrift

A solution of cis (+/−)-benzyl 3-(tert-butoxycarbonylamino)-5-(hydroxymethyl)piperidine-1-carboxylate (1 eq.), perfluorobutanesulfonylfluoride (2 eq.), triethylamine-HF (4 eq.) and triethylamine (6 eq.) in tetrahydrofuran at a concentration of 0.16 M was stirred for 36 hours. Upon dilution with ethyl acetate (50×) the solution was washed with 1N HCl, NaHCO3(sat.) and brine, was dried over MgSO4, filtered, concentrated and purified by column chromatography (25-40% ethyl acetate/hexanes) to yield cis (+/−)-benzyl 3-(tert-butoxycarbonylamino)-5-(fluoromethyl)piperidine-1-carboxylate (45% yield). LCMS (m/z): 267.1 (MH+); LC Rt=4.23 min.

Quelle

DOI: 10.6084/m9.figshare.5104873.v1Patent: US08822497B2uspto-grants-2014_09