Diisopropylamine → 4-[1-Carboxy-2-(4-fluoro-phenyl)-ethyl]-4-hydroxy-piperidine-1-carboxylic acid tert-butyl ester

HRID 12367

Reaktionsgleichung

Reaktionsgleichung von HRID 12367
C([Li])CCC.C(NC(C)C)(C)C.[F:13][C:14]1[CH:19]=[CH:18][C:17]([CH2:20][CH2:21][C:22]([OH:24])=[O:23])=[CH:16][CH:15]=1.[C:25]([N:32]1[CH2:37][CH2:36][C:35](=[O:38])[CH2:34][CH2:33]1)([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26]>C1COCC1.O.C(OCC)C>[C:28]([O:27][C:25]([N:32]1[CH2:37][CH2:36][C:35]([CH:21]([C:22]([OH:24])=[O:23])[CH2:20][C:17]2[CH:16]=[CH:15][C:14]([F:13])=[CH:19][CH:18]=2)([OH:38])[CH2:34][CH2:33]1)=[O:26])([CH3:31])([CH3:29])[CH3:30]

Komponenten

8

Edukt 4

HCID 7912DiisopropylamineHCID 1363023-(4-Fluorophenyl)propionic acidHCID 735900tert-Butyl 4-oxopiperidine-1-carboxylateHCID 178418339Butyllithium

Produkt 1

HCID 574580114-[1-Carboxy-2-(4-fluoro-phenyl)-ethyl]-4-hydroxy-piperidine-1-carboxylic acid tert-butyl ester

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 962WaterLösungsmittelHCID 3283Diethyl EtherLösungsmittelHCID 8028TetrahydrofuranLösungsmittel3×

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

n-Butyllithium (1.6 M in hexane, 8.8 mL, 14.0 mmol) was added dropwise under stirring over 5 min to a cooled solution of N,N-diisopropylamine (2.0 mL, 14.0 mmol) in THF (10 mL) at −40° C. The solution was warmed to 0° C. and a solution of 3-(4-fluoro-phenyl)propionic acid (1.18 g, 7.0 mmol) in THF (8 mL) was added. The mixture was stirred for 30 min at rt, cooled to −78° C. and N-BOC-4-piperidone (1.68 g, 8.4 mmol) in THF (7 mL) added dropwise over 15 min. The solution was allowed to warm to rt and poured into a stirred mixture of diethylether (100 mL) and water (50 mL). The organic layer was discarded, the aqueous layer extracted with another portion of diethylether. The aqueous layer was acidified with 2 M aq. HCl to pH 3.5 and extracted with dichloromethane (3×100 mL). The combined extracts were dried over Na2SO4, filtered and concentrated in vacuo, giving 69NLS56 as a yellow solid, which is used without further purification.

Aufarbeitung

  1. temperaturecooled to −78° C.
  2. temperatureto warm to rt
  3. extractionthe aqueous layer extracted with another portion of diethylether
  4. extractionextracted with dichloromethane (3×100 mL)
  5. dry with materialThe combined extracts were dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo

Quellen und Nachweise

ORD-Eintrag
ord-5149e481278741f7a4613a29de63943b
Quelldatensatz
uspto-grants-2010_06
Patentnummer
US07727999B2

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