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Water → tert-butyl 7-bromo-2-(4-methoxybenzyl)-3-oxo-2',3'-dihydro-1'H-spiro[isoindoline-1,4'-pyridine]-1'-carboxylate

HRID 390136
Notizen
Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 390136
[Br:1][C:2]1[C:3](I)=[C:4]([CH:30]=[CH:31][CH:32]=1)[C:5]([N:7]([C:17]1[CH2:22][CH2:21][N:20]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH2:19][CH:18]=1)[CH2:8][C:9]1[CH:14]=[CH:13][C:12]([O:15][CH3:16])=[CH:11][CH:10]=1)=[O:6].C([O-])([O-])=O.[K+].[K+].C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O>CC#N.[Cl-].C([N+](CCCC)(CCCC)CCCC)CCC.CC([O-])=O.CC([O-])=O.[Pd+2]>[Br:1][C:2]1[CH:32]=[CH:31][CH:30]=[C:4]2[C:3]=1[C:17]1([CH:22]=[CH:21][N:20]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH2:19][CH2:18]1)[N:7]([CH2:8][C:9]1[CH:14]=[CH:13][C:12]([O:15][CH3:16])=[CH:11][CH:10]=1)[C:5]2=[O:6]
KomponentenVersuchsvorschriftAufarbeitungQuellen und NachweiseNotizen zur Reaktion

Komponenten

8

Edukt 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 11776TriphenylphosphineHCID 58295704tert-butyl 4-(3-bromo-2-iodo-N-(4-methoxybenzyl)benzamido)-5,6-dihydropyridine-1(2H)-carboxylate

Produkt 1

HCID 58295753tert-butyl 7-bromo-2-(4-methoxybenzyl)-3-oxo-2',3'-dihydro-1'H-spiro[isoindoline-1,4'-pyridine]-1'-carboxylate
Ausbeute 50,1 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 70681Tetrabutylammonium ChlorideKatalysatorHCID 167845palladium(II) acetateKatalysatorHCID 6342AcetonitrileLösungsmittel

Versuchsvorschrift

A solution of tert-butyl 4-(3-bromo-2-iodo-N-(4-methoxybenzyl)benzamido)-5,6-dihydropyridine-1(2H)-carboxylate (30 g, 0.048 mol) in CH3CN (500 mL) was stirred for 0.5 h under nitrogen. K2CO3 (13 g, 0.096 mol), PPh3 (6 g, 20%), tetra-butylammonium chloride (15 g, 0.048 mol) and Pd(OAc)2 (3 g, 0.0048 mol) were added. The resulting mixture was heated to reflux for 12 h. The mixture was poured into water and extracted with EtOAc. The organic layer was dried and concentrated to give the crude product which was purified by column chromatography to afford tert-butyl 7-bromo-2-(4-methoxybenzyl)-3-oxo-2′,3′-dihydro-1′H-spiro[isoindoline-1,4′-pyridine]-1′-carboxylate (12 g, 50%). 1H NMR: (400 MHz, CDCl3): δ=1.51 (s, 9H), 1.73 (m, 2H), 2.83-3.08 (m, 2H), 3.79 (s, 3H), 4.00 (m, 1H), 4.30 (m, 1H), 4.42 (d, 1H), 5.02 (d, 1H), 6.83 (d, 2H), 7.201 (d, 2H), 7.45 (m, 1H), 7.70 (d, 1H), 7.88 (d, 1H).

Aufarbeitung

  1. temperatureThe resulting mixture was heated
  2. temperatureto reflux for 12 h
  3. extractionextracted with EtOAc
  4. customThe organic layer was dried
  5. concentrationconcentrated
  6. customto give the crude product which
  7. customwas purified by column chromatography

Quellen und Nachweise

ORD-Eintrag
ord-e61d501e87164d19b02516b56f95ff72
Quelldatensatz
uspto-grants-2013_02
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US08383629B2

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