Dimethylformamide → Tert-butyl 2-(4-cyano-1-oxoisoindolin-2-yl)-4-carbamoylbutanoate

HRID 10061

Reaktionsgleichung

Reaktionsgleichung von HRID 10061
Br[C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[CH2:4][N:5]([CH:12]([CH2:20][CH2:21][C:22](=[O:24])[NH2:23])[C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[C:6]2=[O:11].CCOC(C)=O.C([O-])(O)=O.[Na+].[CH3:36][N:37](C=O)C>[Zn].C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2]>[C:36]([C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[CH2:4][N:5]([CH:12]([CH2:20][CH2:21][C:22](=[O:24])[NH2:23])[C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[C:6]2=[O:11])#[N:37]

Komponenten

8

Edukt 4

HCID 6228DimethylformamideHCID 8857Ethyl AcetateHCID 516892Sodium BicarbonateHCID 21988515Tert-butyl 2-(4-bromo-1-oxoisoindolin-2-yl)-4-carbamoylbutanoate

Produkt 1

HCID 21988604Tert-butyl 2-(4-cyano-1-oxoisoindolin-2-yl)-4-carbamoylbutanoateAusbeute 74 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 23994ZincKatalysatorHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)KatalysatorHCID 9811564Bis(dibenzylideneacetone)palladiumKatalysator

Reaktionsbedingungen

Temperatur
120 °C

Versuchsvorschrift

A mixture of tert-butyl 2-(4-bromo-1-oxoisoindolin-2-yl)-4-carbamoylbutanoate (1.2 g, 3.02 mmol), zinc cyamide (0.21 g, 1.81 mmol), tris(dibenzylideneacetone)dipalladium (0.06 g, 0.06 mmol), 1,1′-bis(diphenylphosphino)ferrocene (0.067 g, 0.12 mmol) in deoxygenated DMF (15 mL) was heated to 120° C. under N2 for 6 hours. The mixture was cooled to room temperature and poured into EtOAc (100 mL) and sat. NaHCO3 (40 mL). The EtOAc solution was washed with water (2×40 mL), brine (40 mL), and dried (MgSO4). Solvent was removed and the residue was purified by chromatography (CH2Cl2:CH3OH 97.5:2.5) to afford tert-butyl 2-(4-cyano-1-oxoisoindolin-2-yl)-4-carbamoylbutanoate (0.77 g, 74%): 1H NMR (CDCl3) δ 8.07–8.03 (dd, J=0.7 and 7.4 Hz, 1H), 7.86–7.83 (dd, J=1.0 and 7.9 Hz, 1H), 7.61 (t, J=7.6 Hz, 1H), 5.91 (s, 1H), 5.68 (s, 1H), 5.03–4.98 (m, 1H), 4.85 (d, J=17.9 Hz, 1H), 4.62 (d, J=17.9 Hz, 1H), 2.48–2.41(m, 4H), 1.46 (s, 9H); 13C NMR (CDCl3) δ 173.56, 169.21, 167.70, 145.23, 134.94, 133.11, 128.93, 128.21, 115.65, 107.86, 82.98, 63.68, 54.47, 46.55, 32.34, 27.95, 25.46.

Aufarbeitung

  1. temperatureThe mixture was cooled to room temperature
  2. washThe EtOAc solution was washed with water (2×40 mL), brine (40 mL)
  3. dry with materialdried (MgSO4)
  4. customSolvent was removed
  5. customthe residue was purified by chromatography (CH2Cl2:CH3OH 97.5:2.5)

Quellen und Nachweise

ORD-Eintrag
ord-cb213946227849cba6cbc5d842b1724b
Quelldatensatz
uspto-grants-2006_08
Patentnummer
US07091353B2

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