Triethylamine → (3S,5R)-benzyl 3-azido-5-fluoropiperidine-1-carboxylate

HRID 73541Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 73541
[F:1][C@@H:2]1[CH2:7][C@@H:6](O)[CH2:5][N:4]([C:9]([O:11][CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=[O:10])[CH2:3]1.C(N(CC)CC)C.CS(Cl)(=O)=O.[N-:31]=[N+:32]=[N-:33].[Na+]>ClCCl.C(OCC)C.CCOC(C)=O>[N:31]([C@H:6]1[CH2:7][C@@H:2]([F:1])[CH2:3][N:4]([C:9]([O:11][CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=[O:10])[CH2:5]1)=[N+:32]=[N-:33]

Komponenten

8

Edukt 4

HCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 33557Sodium AzideHCID 59455657HCID 59455657, Verbindung

Produkt 1

HCID 59455729(3S,5R)-benzyl 3-azido-5-fluoropiperidine-1-carboxylateAusbeute 90 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 3283Diethyl EtherLösungsmittelHCID 6344DichloromethaneLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

To a solution of (3R,5R)-benzyl 3-fluoro-5-hydroxypiperidine-1-carboxylate (1 eq) in 14 mL of dichloromethane was added triethyl amine (3 eq) and methanesulfonyl chloride (1.5 eq) at 0° C. The reaction mixture was allowed to stir at room temperature for 1.5 hours. The crude mixture was diluted with 120 mL of diethyl ether, washed with sat. aq. sodium bicarbonate, brine, then dried over anhydrous MgSO4, filtered, and concentrated in vacuo. The crude residue was dissolved in 16 mL of NMP. Sodium azide (3.0 eq) was added and the resulting suspension was stirred at 80° C. overnight. The reaction mixture was diluted with 200 mL of EtOAc and 100 mL of hexanes, washed with water, brine, then dried over anhydrous MgSO4, filtered, and concentrated in vacuo. The crude residue was purified by flash chromatography (EtOAc:hexanes=1:3) to yield (3S,5R)-benzyl 3-azido-5-fluoropiperidine-1-carboxylate (90%). LC/MS (m/z): 251.1 (MH+-28).

Aufarbeitung

  1. washwashed with sat. aq. sodium bicarbonate, brine
  2. dry with materialdried over anhydrous MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. dissolutionThe crude residue was dissolved in 16 mL of NMP
  6. stirringthe resulting suspension was stirred at 80° C. overnight
  7. washwashed with water, brine
  8. dry with materialdried over anhydrous MgSO4
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customThe crude residue was purified by flash chromatography (EtOAc:hexanes=1:3)

Quellen und Nachweise

ORD-Eintrag
ord-8b5091c2a50d448cb1c0b939bd06ecbf
Quelldatensatz
uspto-grants-2014_09
Patentnummer
US08829193B2

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