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

HRID 409934ノート

反応式

HRID 409934 の反応式
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

参加物

10

反応物 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

生成物 1

HCID 247886951-[2-Fluoro-4-(2-phenoxycarbonylaminopyridin-4-yloxy)phenylcarbamoyl]cyclopropanecarboxylic acid benzyl ester収率 99.1%

試薬・触媒・溶媒 5

HCID 962Water溶媒HCID 1049Pyridine溶媒HCID 6342Acetonitrile溶媒2 回HCID 8028Tetrahydrofuran溶媒2 回HCID 16069498Pyridine tetrahydrofuran溶媒

反応条件

温度
10 °C

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-9bd1752451df4aecb56345e090f1f0e9
出典データセット
uspto-grants-2014_06
特許番号
US08759530B2

反応ノート

読み込み中…