Phenyl chloroformate → 1-[2-Fluoro-4-(2-phenoxycarbonylaminopyridin-4-yloxy)phenylcarbamoyl]cyclopropanecarboxylic acid benzyl ester

HRID 409934Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 409934
Cl[C:2]([O:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)=[O:3].[CH2:11]([O:18][C:19]([C:21]1([C:24](=[O:41])[NH:25][C:26]2[CH:31]=[CH:30][C:29]([O:32][C:33]3[CH:38]=[CH:37][N:36]=[C:35]([NH2:39])[CH:34]=3)=[CH:28][C:27]=2[F:40])[CH2:23][CH2:22]1)=[O:20])[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.ClC(OC1C=CC=CC=1)=O.C(#N)C.C(OC(C1(C(=O)NC2C=CC(OC3C=CN=C(N)C=3)=CC=2F)CC1)=O)C1C=CC=CC=1.O1CCCC1>C(#N)C.O1CCCC1.O.O1CCCC1.N1C=CC=CC=1.N1C=CC=CC=1>[CH2:11]([O:18][C:19]([C:21]1([C:24](=[O:41])[NH:25][C:26]2[CH:31]=[CH:30][C:29]([O:32][C:33]3[CH:38]=[CH:37][N:36]=[C:35]([NH:39][C:2]([O:4][C:5]4[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=4)=[O:3])[CH:34]=3)=[CH:28][C:27]=2[F:40])[CH2:22][CH2:23]1)=[O:20])[C:12]1[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=1

Komponenten

10

Edukt 4

HCID 15891Phenyl chloroformateHCID 594597071-[4-(2-Aminopyridin-4-yloxy)-2-fluorophenylcarbamoyl]cyclopropanecarboxylic acid benzyl esterHCID 86707875Phenyl chloroformate acetonitrileHCID 867078761-[4-(2-Aminopyridin-4-yloxy)-2-fluorophenylcarbamoyl]cyclopropanecarboxylic acid benzyl ester tetrahydrofuran

Produkt 1

HCID 247886951-[2-Fluoro-4-(2-phenoxycarbonylaminopyridin-4-yloxy)phenylcarbamoyl]cyclopropanecarboxylic acid benzyl esterAusbeute 99,1 %

Reagenzien, Katalysatoren, Lösungsmittel 5

HCID 962WaterLösungsmittelHCID 1049PyridineLösungsmittelHCID 6342AcetonitrileLösungsmittel2×HCID 8028TetrahydrofuranLösungsmittel2×HCID 16069498Pyridine tetrahydrofuranLösungsmittel

Reaktionsbedingungen

Temperatur
10 °C

Versuchsvorschrift

Pyridine (50 ml) was mixed with tetrahydrofuran (40 ml) and cooled to 10° C. A solution of phenyl chloroformate (4.83 g) in acetonitrile (50 ml) and a solution of 1-[4-(2-aminopyridin-4-yloxy)-2-fluorophenylcarbamoyl]cyclopropanecarboxylic acid benzyl ester (10.00 g) in tetrahydrofuran (80 ml) were added dropwise to the tetrahydrofuran-pyridine solution over a period of 2 hours at 10° C. At this time, the amounts of the phenyl chloroformate-acetonitrile solution and the 1-[4-(2-aminopyridin-4-yloxy)-2-fluorophenylcarbamoyl]cyclopropanecarboxylic acid benzyl ester/tetrahydrofuran solution added dropwise were adjusted to the constant rate so that each solution was added dropwise over a period of 2 hours. The crystals were precipitated while the solutions were added dropwise. After completing the dropwise addition, the completion of reaction was confirmed using an HPLC apparatus. Subsequently, a mixed solution of water (10 ml) and acetonitrile (50 ml) was added to the reaction mixture. The crystals were collected by filtration and washed with a mixed solution of tetrahydrofuran (15 ml)-acetonitrile (15 ml) and dried under reduced pressure to give the title compound (12.74 g). Apparent yield 98.0%, purity 94.6% (HPLC area percentage).

Aufarbeitung

  1. additionwas added dropwise over a period of 2 hours
  2. customThe crystals were precipitated while the solutions
  3. additionwere added dropwise
  4. additionthe dropwise addition
  5. customthe completion of reaction
  6. filtrationThe crystals were collected by filtration
  7. washwashed with a mixed solution of tetrahydrofuran (15 ml)-acetonitrile (15 ml)
  8. customdried under reduced pressure

Quellen und Nachweise

ORD-Eintrag
ord-9bd1752451df4aecb56345e090f1f0e9
Quelldatensatz
uspto-grants-2014_06
Patentnummer
US08759530B2

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