Sodium Hydroxide → (2S,4R)-2-(3,5-Bis-trifluoromethyl-phenyl)-N-[3-chloro-6'-(4-hydroxy-2-hydroxymethyl-pyrrolidin-1-yl)-[2,4']bipyridinyl-3'-yl]-N-methyl-isobutyramide

HRID 1951697Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1951697
[Cl:1][C:2]1[C:3](I)=[N:4][CH:5]=[CH:6][CH:7]=1.C([Mg]Cl)(C)C.[F:14][C:15]([F:49])([F:48])[C:16]1[CH:17]=[C:18]([C:26]([CH3:47])([CH3:46])[C:27]([N:29]([C:31]2[CH:32]=[N:33][C:34]([N:38]3[CH2:42][C@H:41]([OH:43])[CH2:40][C@H:39]3[CH2:44][OH:45])=[CH:35][C:36]=2I)[CH3:30])=[O:28])[CH:19]=[C:20]([C:22]([F:25])([F:24])[F:23])[CH:21]=1.[OH-].[Na+]>O1CCCC1.[Cl-].[Zn+2].[Cl-].C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[F:25][C:22]([F:23])([F:24])[C:20]1[CH:19]=[C:18]([C:26]([CH3:46])([CH3:47])[C:27]([N:29]([C:31]2[CH:32]=[N:33][C:34]([N:38]3[CH2:42][C@H:41]([OH:43])[CH2:40][C@H:39]3[CH2:44][OH:45])=[CH:35][C:36]=2[C:3]2[C:2]([Cl:1])=[CH:7][CH:6]=[CH:5][N:4]=2)[CH3:30])=[O:28])[CH:17]=[C:16]([C:15]([F:49])([F:14])[F:48])[CH:21]=1

Komponenten

8

Edukt 4

HCID 14798Sodium HydroxideHCID 108476073-Chloro-2-iodopyridineHCID 86597685HCID 86597685, VerbindungHCID 178418918HCID 178418918, Verbindung

Produkt 1

HCID 86597691(2S,4R)-2-(3,5-Bis-trifluoromethyl-phenyl)-N-[3-chloro-6'-(4-hydroxy-2-hydroxymethyl-pyrrolidin-1-yl)-[2,4']bipyridinyl-3'-yl]-N-methyl-isobutyramideAusbeute 40 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 3007855ZincchlorideKatalysatorHCID 178418397HCID 178418397, VerbindungKatalysatorHCID 8028TetrahydrofuranLösungsmittel4×

Versuchsvorschrift

To a solution of 0.500 g (2.09 mmol) 3-chloro-2-iodo-pyridine in 6 ml tetrahydrofuran 1.04 ml (2.09 mmol) of a 2 M solution of isopropylmagnesium chloride in tetrahydrofuran was added dropwise at −40° C. under an atmosphere of argon. After 30 min. 2.3 ml (4.2 mmol) of an anhydrous 1.8 M solution of zinc chloride in tetrahydrofuran was added slowly. The cooling bath was removed after completed addition, and the reaction mixture was stirred at room temperature for 90 min. A portion of 1.6 ml of this solution was added to a solution of 0.15 g (0.24 mmol) (2S,4R)-2-(3,5-bis-trifluoromethyl-phenyl)-N-[6-(4-hydroxy-2-hydroxymethyl-pyrrolidin-1-yl)-4-iodo-pyridin-3-yl]-N-methyl-isobutyramide and 14 mg (0.012 mmol) tetrakis(triphenylphosphine)palladium(0) in 1 ml tetrahydrofuran. The mixture was heated at 100° C. under microwave irradiation for 30 min. After cooling to room temperature a 0.5 M solution of sodium hydroxide was added, and the mixture was extracted with three portions of dichloromethane. The combined organic layers were dried over sodium sulfate and concentrated in vacuo. Flash column chromatography gave 58 mg (40%) of the title compound as a light yellow solid.

Aufarbeitung

  1. customThe cooling bath was removed
  2. additionaddition
  3. temperatureThe mixture was heated at 100° C. under microwave irradiation for 30 min
  4. additionwas added
  5. extractionthe mixture was extracted with three portions of dichloromethane
  6. dry with materialThe combined organic layers were dried over sodium sulfate
  7. concentrationconcentrated in vacuo

Quellen und Nachweise

ORD-Eintrag
ord-c7b2d7544bc4414b9e447f619acb3768
Quelldatensatz
uspto-grants-2013_03
Patentnummer
US08404708B2

Notizen zur Reaktion

Wird geladen…