Methanamine, N-methoxy-, hydrochloride (1:1) → 1-(4-chloro-3-methoxyphenyl)-N-methoxy-N-methylpiperidine-4-carboxamide

HRID 1804849Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1804849
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:13][CH2:12][CH:11]([C:14]([OH:16])=O)[CH2:10][CH2:9]2)=[CH:4][C:3]=1[O:17][CH3:18].Cl.[CH3:20][NH:21][O:22][CH3:23].Cl.C(N=C=NCCCN(C)C)C.C(N(CC)C(C)C)(C)C>CN(C)C1C=CN=CC=1.C(Cl)Cl>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:9][CH2:10][CH:11]([C:14]([N:21]([O:22][CH3:23])[CH3:20])=[O:16])[CH2:12][CH2:13]2)=[CH:4][C:3]=1[O:17][CH3:18]

Komponenten

7

Edukt 4

HCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 68552816HCID 68552816, Verbindung

Produkt 1

HCID 866398021-(4-chloro-3-methoxyphenyl)-N-methoxy-N-methylpiperidine-4-carboxamide

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 142844-(Dimethylamino)pyridineKatalysatorHCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

A mixture of 1-(4-chloro-3-methoxyphenyl)piperidine-4-carboxylic acid (9.0 g, 33.4 mmol), N,O-dimethylhydroxylamine hydrochloride (4.88 g, 50.1 mmol) and DCM (15 mL) was treated with 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (9.59 g, 50.1 mmol) and 4-(dimethylamino)pyridine (0.408 g, 3.34 mmol). The mixture was cooled in an ice bath and treated with N,N-diisopropylethylamine (11.62 mL, 66.7 mmol) over 3 min. After 10 min, the cooling bath was removed and the mixture was stirred at RT overnight (ca. 14 h). At the conclusion of this period, the mixture was diluted with DCM (50 mL), and then washed successively with saturated NaHCO3 (3×25 mL), 1 M HCl (2×50 mL) and brine. The organic phase was dried (MgSO4) and concentrated in vacuo. The resultant residue was purified by flash chromatography using a 120 g silica gel cartridge and 10:1 Hex/EtOAc to elute the product. The fractions containing the product were pooled and concentrated on a rotary evaporator to give 1-(4-chloro-3-methoxyphenyl)-N-methoxy-N-methylpiperidine-4-carboxamide as pale yellow oil.

Aufarbeitung

  1. temperatureThe mixture was cooled in an ice bath
  2. customthe cooling bath was removed
  3. additionAt the conclusion of this period, the mixture was diluted with DCM (50 mL)
  4. washwashed successively with saturated NaHCO3 (3×25 mL), 1 M HCl (2×50 mL) and brine
  5. dry with materialThe organic phase was dried (MgSO4)
  6. concentrationconcentrated in vacuo
  7. customThe resultant residue was purified by flash chromatography
  8. washto elute the product
  9. additionThe fractions containing the product
  10. concentrationconcentrated on a rotary evaporator

Quellen und Nachweise

ORD-Eintrag
ord-84f0feca37084f3ca12dbdb55825ae06
Quelldatensatz
uspto-grants-2013_01
Patentnummer
US08354432B2

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