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Ammonium Chloride → Tert-butyl 1-(3-{[(4-chlorophenyl)(2,2-difluorocyclopentyl)acetyl]amino}-4-fluorobenzyl)cyclopropanecarboxylate

HRID 1475661
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Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 1475661
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([CH:12]2[CH2:16][CH2:15][CH2:14][C:13]2([F:18])[F:17])[C:9]([OH:11])=O)=[CH:4][CH:3]=1.[NH2:19][C:20]1[CH:21]=[C:22]([CH:34]=[CH:35][C:36]=1[F:37])[CH2:23][C:24]1([C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[CH2:26][CH2:25]1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[Cl-].[NH4+]>C(#N)C.O.N1C=CC=CC=1.CN(C=O)C>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([CH:8]([CH:12]2[CH2:16][CH2:15][CH2:14][C:13]2([F:18])[F:17])[C:9]([NH:19][C:20]2[CH:21]=[C:22]([CH:34]=[CH:35][C:36]=2[F:37])[CH2:23][C:24]2([C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[CH2:25][CH2:26]2)=[O:11])=[CH:6][CH:7]=1
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Komponenten

8

Edukt 4

HCID 25517Ammonium ChlorideHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 58136688tert-Butyl 1-(3-amino-4-fluorobenzyl)cyclopropanecarboxylateHCID 58288424(4-chlorophenyl)(2,2-difluorocyclopentyl)acetic Acid

Produkt 1

HCID 66563456
Tert-butyl 1-(3-{[(4-chlorophenyl)(2,2-difluorocyclopentyl)acetyl]amino}-4-fluorobenzyl)cyclopropanecarboxylate

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 1049PyridineLösungsmittelHCID 6228DimethylformamideLösungsmittelHCID 18373917Acetonitrile--water (1/1)Lösungsmittel

Versuchsvorschrift

490 mg (1.78 mmol) of (4-chlorophenyl)(2,2-difluorocyclopentyl)acetic acid (as diastereomer mixture) were added to a mixture of 4.0 ml of DMF and 1.0 ml of pyridine. At RT, 568.0 mg (2.14 mmol) of tert-butyl 1-(3-amino-4-fluorobenzyl)cyclopropanecarboxylate and 881.7 mg (2.34 mmol) of HATU were added to the resulting solution and the mixture was stirred at RT overnight. The reaction mixture was then added to saturated aqueous ammonium chloride solution and extracted three times with ethyl acetate. The combined organic phases were dried over magnesium sulphate and concentrated under reduced pressure. The crude product was purified by chromatography on silica gel (mobile phase cyclohexane/ethyl acetate 20:1). Further purification of the product obtained in this manner was carried out by preparative RP-HPLC (mobile phase acetonitrile/water). This gave 774.0 mg (83.1% of theory) of the target compound.

Aufarbeitung

  1. extractionextracted three times with ethyl acetate
  2. dry with materialThe combined organic phases were dried over magnesium sulphate
  3. concentrationconcentrated under reduced pressure
  4. customThe crude product was purified by chromatography on silica gel (mobile phase cyclohexane/ethyl acetate 20:1)
  5. customFurther purification of the product
  6. customobtained in this manner

Quellen und Nachweise

ORD-Eintrag
ord-f81ca0a8abf1458288f02dd719901b21
Quelldatensatz
uspto-grants-2015_04
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US09018258B2

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