Triethylamine → Methyl 1-{[(4,4'-dichlorobiphenyl-3-yl)acetyl]amino}-4,4-difluorocyclohexanecarboxylate

HRID 1466450Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1466450
Cl.[NH2:2][C:3]1([C:11]([O:13][CH3:14])=[O:12])[CH2:8][CH2:7][C:6]([F:10])([F:9])[CH2:5][CH2:4]1.C(N(CC)CC)C.[Cl:22][C:23]1[CH:28]=[CH:27][C:26]([C:29]2[CH:34]=[CH:33][C:32]([Cl:35])=[CH:31][CH:30]=2)=[CH:25][C:24]=1[CH2:36][C:37](O)=[O:38].P(Cl)(Cl)(Cl)=O>O1CCCC1>[Cl:22][C:23]1[CH:28]=[CH:27][C:26]([C:29]2[CH:30]=[CH:31][C:32]([Cl:35])=[CH:33][CH:34]=2)=[CH:25][C:24]=1[CH2:36][C:37]([NH:2][C:3]1([C:11]([O:13][CH3:14])=[O:12])[CH2:8][CH2:7][C:6]([F:10])([F:9])[CH2:5][CH2:4]1)=[O:38]

Komponenten

6

Edukt 4

HCID 8471Triethylamine2×HCID 24813Phosphorus oxychlorideHCID 60196672Methyl 1-amino-4,4-difluorocyclohexanecarboxylate hydrochlorideHCID 67372946(4,4'-Dichlorobiphenyl-3-yl)acetic acid

Produkt 1

HCID 86707850Methyl 1-{[(4,4'-dichlorobiphenyl-3-yl)acetyl]amino}-4,4-difluorocyclohexanecarboxylate

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

2.53 g (11 mmol) of the compound from Example 4A were initially charged in 50 ml of absolute tetrahydrofuran (THF). 3.07 ml of triethylamine were added dropwise at 20° C., the mixture was stirred for 5 min, and 2.81 g (10 mmol) of (4,4′-dichlorobiphenyl-3-yl)acetic acid (EP 1943218 A1 and US 2009/215624 A1) were added. After 15 min, a further 2.3 ml of triethylamine were added, followed immediately by the dropwise addition of 0.58 ml (6.2 mmol) of phosphorus oxychloride, and the mixture was stirred under reflux for 30 min. The mixture was concentrated under reduced pressure and the residue was purified by means of flash chromatography on silica gel using the mobile phase n-hexane/ethyl acetate 1:1. This gave 3.3 g (59% of theory) of the title compound of melting point 146-147° C.

Aufarbeitung

  1. waitAfter 15 min
  2. stirringthe mixture was stirred
  3. temperatureunder reflux for 30 min
  4. concentrationThe mixture was concentrated under reduced pressure
  5. customthe residue was purified by means of flash chromatography on silica gel using the mobile phase n-hexane/ethyl acetate 1:1

Quellen und Nachweise

ORD-Eintrag
ord-187b1c4383c34993b8ae21a9b59c1cbf
Quelldatensatz
uspto-grants-2015_04
Patentnummer
US09000026B2

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