Sodium Cyanide → (1R,2R)-methyl-3-((2-(4-cyanophenyl)-5'-fluoro-2-isopropyl-2'-oxospiro[cyclopropane-1,3'-indoline]-1'-yl)methyl)benzoate

HRID 1805311Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1805311
[CH3:1][O:2][C:3](=[O:34])[C:4]1[CH:9]=[CH:8][CH:7]=[C:6]([CH2:10][N:11]2[C:19]3[C:14](=[CH:15][C:16]([F:20])=[CH:17][CH:18]=3)[C@:13]3([CH2:22][C@:21]3([C:26]3[CH:31]=[CH:30][C:29](I)=[CH:28][CH:27]=3)[CH:23]([CH3:25])[CH3:24])[C:12]2=[O:33])[CH:5]=1.[C-:35]#[N:36].[Na+]>O1CCCC1.[Cu]I.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>[CH3:1][O:2][C:3](=[O:34])[C:4]1[CH:9]=[CH:8][CH:7]=[C:6]([CH2:10][N:11]2[C:19]3[C:14](=[CH:15][C:16]([F:20])=[CH:17][CH:18]=3)[C@:13]3([CH2:22][C@:21]3([C:26]3[CH:31]=[CH:30][C:29]([C:35]#[N:36])=[CH:28][CH:27]=3)[CH:23]([CH3:25])[CH3:24])[C:12]2=[O:33])[CH:5]=1

Komponenten

6

Edukt 2

HCID 8929Sodium CyanideHCID 58305329(1R,2R)-methyl-3-((-5'-fluoro-2-(4-iodophenyl)-2-isopropyl-2'-oxospiro[cyclopropane-1,3'-indoline]-1'-yl)methyl)benzoate

Produkt 1

HCID 67235156(1R,2R)-methyl-3-((2-(4-cyanophenyl)-5'-fluoro-2-isopropyl-2'-oxospiro[cyclopropane-1,3'-indoline]-1'-yl)methyl)benzoateAusbeute 45,5 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)KatalysatorHCID 178418397HCID 178418397, VerbindungKatalysatorHCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

A solution of (1S,2S) and (1R,2R)-methyl-3-((-5′-fluoro-2-(4-iodophenyl)-2-isopropyl-2′-oxospiro[cyclopropane-1,3′-indoline]-1′-yl)methyl)benzoate (1.35 g, 2.4 mmol), NaCN (240 mg, 4.9 mmol), CuI (50 mg, 0.3 mmol) and Pd(PPh3)4 (140 mg, 0.12 mmol) in tetrahydrofuran (9.0 mL) was stirred at 65° C. for 2 hours. The mixture was cooled to room temperature and extracted with ethyl acetate and washed with brine, dried over anhydrous sodium sulfate, concentrated in vacuo. Purification by flash column chromatography eluting with Hexane/ethyl acetate (8:1 to 4:1) to afford light yellow oil (500 mg, yield 45.5%) LC/MS m/e calcd. for C29H25FN2O3: 469, observed (M+H)+: 469.2

Aufarbeitung

  1. extractionextracted with ethyl acetate
  2. washwashed with brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. concentrationconcentrated in vacuo
  5. customPurification by flash column chromatography
  6. washeluting with Hexane/ethyl acetate (8:1 to 4:1)

Quellen und Nachweise

ORD-Eintrag
ord-e7a9ea233f9e41978830b482c75003cc
Quelldatensatz
uspto-grants-2013_01
Patentnummer
US08354443B2

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