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

HRID 1475661
ノート
印刷プレビュー

反応式

HRID 1475661 の反応式
[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
参加物実験手順後処理出典と根拠反応ノート

参加物

8

反応物 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

生成物 1

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

試薬・触媒・溶媒 3

HCID 1049Pyridine溶媒HCID 6228Dimethylformamide溶媒HCID 18373917Acetonitrile--water (1/1)溶媒

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-f81ca0a8abf1458288f02dd719901b21
出典データセット
uspto-grants-2015_04
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US09018258B2

反応ノート

読み込み中…

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