Acetic Acid → Ethyl 6-{(E)-2-[3-(difluoromethoxy)-2-hydroxyphenyl]vinyl}imidazo[2,1-b][1,3]thiazole-5-carboxylate

HRID 1882138Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1882138
C1([O:6][C:7]2[C:12]([O:13][CH:14]([F:16])[F:15])=[CH:11][CH:10]=[CH:9][C:8]=2/[CH:17]=[CH:18]/[C:19]2[N:20]=[C:21]3[N:25]([C:26]=2[C:27]([O:29][CH2:30][CH3:31])=[O:28])[CH:24]=[CH:23][S:22]3)CCCC1.C1(OC2C(OC(F)F)=CC=CC=2/C=C/C2N=C3N(C=2C(O)=O)C=CS3)CCCC1.C(O)(=O)C.C([O-])(O)=O.[Na+]>Br>[F:16][CH:14]([F:15])[O:13][C:12]1[C:7]([OH:6])=[C:8](/[CH:17]=[CH:18]/[C:19]2[N:20]=[C:21]3[N:25]([C:26]=2[C:27]([O:29][CH2:30][CH3:31])=[O:28])[CH:24]=[CH:23][S:22]3)[CH:9]=[CH:10][CH:11]=1

Komponenten

6

Edukt 4

HCID 176Acetic AcidHCID 516892Sodium BicarbonateHCID 593699436-{(E)-2-[2-(Cyclopentyloxy)-3-(difluoromethoxy)phenyl]vinyl}imidazo[2,1-b][1,3]thiazole-5-carboxylic acidHCID 67549214Ethyl 6-{(E)-2-[2-(cyclopentyloxy)-3-(difluoromethoxy)phenyl]vinyl}imidazo[2,1-b][1,3]thiazole-5-carboxylate

Produkt 1

HCID 59369921Ethyl 6-{(E)-2-[3-(difluoromethoxy)-2-hydroxyphenyl]vinyl}imidazo[2,1-b][1,3]thiazole-5-carboxylateAusbeute 86,2 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 260Hydrogen BromideLösungsmittel

Reaktionsbedingungen

Temperatur
60 °C

Versuchsvorschrift

A solution of Ethyl 6-{(E)-2-[2-(cyclopentyloxy)-3-(difluoromethoxy)phenyl]vinyl}imidazo[2,1-b][1,3]thiazole-5-carboxylate (4.10 g, 9.149 mmol) from Intermediate 5, Step 1 in a mixture of 48% hydrobromic acid (20 mL) and glacial acetic acid (20 mL) was heated at 60° C. for 2 h. The reaction mixture was cooled to room temperature and neutralized with saturated solution of NaHCO3. The mixture was extracted with ethyl acetate (2×100 mL) and the combined organic layers were washed with water (2×100 mL), dried over anhydrous Na2SO4. The residue obtained after the evaporation of the solvent was purified by silica gel column chromatography using 2% ethyl acetate in petroleum ether to obtain 3.0 g of the product as an off-white solid; 1H NMR (300 MHz, DMSO-d6) δ 1.40 (t, J=6.3 Hz, 3H), 4.34-4.43 (m, 2H), 6.80-6.90 (m, 1H), 7.05-7.10 (m, 1H), 7.12 (t, J=69.0 Hz, 1H), 7.40-7.48 (m, 2H), 7.78 (d, J=16.2 Hz, 1H), 7.87 (d, J=16.2 Hz, 1H), 8.10-8.16 (m, 1H), 9.79 (br s, 1H); APCI-MS (m/z) 381.15 (MH)+.

Aufarbeitung

  1. extractionThe mixture was extracted with ethyl acetate (2×100 mL)
  2. washthe combined organic layers were washed with water (2×100 mL)
  3. dry with materialdried over anhydrous Na2SO4
  4. customThe residue obtained
  5. customafter the evaporation of the solvent
  6. customwas purified by silica gel column chromatography

Quellen und Nachweise

ORD-Eintrag
ord-0e826e62c22e4d60a7fd633f678866d4
Quelldatensatz
uspto-grants-2012_11
Patentnummer
US08318928B2

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