Triethylamine → 4-[2-(5-Bromo-4-fluoro-2-methyl-phenyl)-acetylamino]-1-methoxy-piperidine-4-carboxylic acid methyl ester

HRID 1962375Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1962375
[Br:1][C:2]1[C:3]([F:13])=[CH:4][C:5]([CH3:12])=[C:6]([CH2:8][C:9]([OH:11])=O)[CH:7]=1.C(N1C=CN=C1)(N1C=CN=C1)=O.C(N(CC)CC)C.Cl.[CH3:34][O:35][C:36]([C:38]1([NH2:46])[CH2:43][CH2:42][N:41]([O:44][CH3:45])[CH2:40][CH2:39]1)=[O:37]>O1CCCC1>[CH3:34][O:35][C:36]([C:38]1([NH:46][C:9](=[O:11])[CH2:8][C:6]2[CH:7]=[C:2]([Br:1])[C:3]([F:13])=[CH:4][C:5]=2[CH3:12])[CH2:43][CH2:42][N:41]([O:44][CH3:45])[CH2:40][CH2:39]1)=[O:37]

Komponenten

6

Edukt 4

HCID 8471TriethylamineHCID 682631,1'-CarbonyldiimidazoleHCID 596146012-(5-Bromo-4-fluoro-2-methylphenyl)acetic acidHCID 666317834-Amino-1-methoxy-piperidine-4-carboxylic acid methyl ester hydrochloride

Produkt 1

HCID 596145984-[2-(5-Bromo-4-fluoro-2-methyl-phenyl)-acetylamino]-1-methoxy-piperidine-4-carboxylic acid methyl ester

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

A suspension of (5-bromo-4-fluoro-2-methyl-phenyl)-acetic acid (preparation example P5.3) (8.0 g) and 1,1′-carbonyldiimidazole (5.8 g) in tetrahydrofuran (150 ml) was heated at reflux for 30 minutes. Upon cooling to room temperature, triethylamine (9.0 ml) and 4-amino-1-methoxy-piperidine-4-carboxylic acid methyl ester hydrochloride salt (preparation example P1, step P1.3) (13.8 g) were added and warming at reflux was continued for 3 hours. The cold reaction mixture was poured on water/ethyl acetate, the layers separated, the organic phase washed with brine, dried over sodium sulfate and concentrated. The residue was solubilised in ethyl acetate/cyclohexane 3:1 and purified by filtration on alumina. Yield: 6.83 g of 4-[2-(5-bromo-4-fluoro-2-methyl-phenyl)-acetylamino]-1-methoxy-piperidine-4-carboxylic acid methyl ester as a solid, mp: 192-193° C.

Aufarbeitung

  1. temperaturewas heated
  2. temperatureat reflux for 30 minutes
  3. temperaturewarming
  4. temperatureat reflux
  5. customThe cold reaction mixture
  6. additionwas poured on water/ethyl acetate
  7. customthe layers separated
  8. washthe organic phase washed with brine
  9. dry with materialdried over sodium sulfate
  10. concentrationconcentrated
  11. filtrationpurified by filtration on alumina

Quellen und Nachweise

ORD-Eintrag
ord-726aca880f3e4f55afcd3871a43e90be
Quelldatensatz
uspto-grants-2013_04
Patentnummer
US08415369B2

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