Tert-Butyl nitrite → 2-[(2-bromo-1,3-thiazol-4-yl)methoxy]-1H-isoindole-1,3(2H)-dione

HRID 2039681

Reaktionsgleichung

N[C:2]1[S:3][CH:4]=[C:5]([CH2:7][O:8][N:9]2[C:17](=[O:18])[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=3)[C:10]2=[O:19])[N:6]=1.[Na+].[Br-:21].N(OC(C)(C)C)=O>C(#N)C.O>[Br:21][C:2]1[S:3][CH:4]=[C:5]([CH2:7][O:8][N:9]2[C:17](=[O:18])[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=3)[C:10]2=[O:19])[N:6]=1

Komponenten

Reaktionsbedingungen

Temperatur: 65 °C

Versuchsvorschrift

To a suspension of 2-[(2-amino-1,3-thiazol-4-yl)methoxy]-1H-isoindole-1,3(2H)-dione (4.13 g, 15 mmol), NaBr (3.10 g, 30 mmol) and CuBr (2.15 g, 15 mmol) in acetonitrile (150 mL) at 40° C. under nitrogen atmosphere was added tert-butyl nitrite (2.32 mL, 19.5 mmol) dropwise over 30-40 min. After the addition was complete, heating was maintained towards an internal temp of 60-70° C., and the suspension was stirred at this temperature for 2 h. After cooling down, the mixture was diluted with water, and extracted with ethyl acetate. The combined organic layers (200 mL) were washed with aq HCl (1M, 50 mL), then with brine (50 mL) and dried (MgSO4). After concentration on the rotary evaporator, the residue was purified on silica gel to afford 2-[(2-bromo-1,3-thiazol-4-yl)methoxy]-1H-isoindole-1,3(2H)-dione [1.50 g, yield 28%; HPLC/MS: m/z=339 (M+H); log P(HCOOH)=2.39].

Aufarbeitung

additionAfter the addition
temperatureheating
temperatureAfter cooling down
extractionextracted with ethyl acetate
washThe combined organic layers (200 mL) were washed with aq HCl (1M, 50 mL)
dry with materialwith brine (50 mL) and dried (MgSO4)
concentrationAfter concentration
customon the rotary evaporator
customthe residue was purified on silica gel

Quellen und Nachweise

ORD-Eintrag: ord-b62db32536984e8b88dc5bf5742e7dd1
Quelldatensatz: uspto-grants-2013_11
DOI: 10.6084/m9.figshare.5104873.v1
Patentnummer: US08580799B2

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