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

HRID 1882138Notes

Reaction equation

HRID 1882138 reaction equation
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

Participants

6

Reactant 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

Product 1

HCID 59369921Ethyl 6-{(E)-2-[3-(difluoromethoxy)-2-hydroxyphenyl]vinyl}imidazo[2,1-b][1,3]thiazole-5-carboxylateYield 86.2%

Reagents, catalysts & solvents 1

HCID 260Hydrogen BromideSolvent

Conditions

Temperature
60 °C

Procedure

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)+.

Workup

  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

Sources & evidence

ORD record
ord-0e826e62c22e4d60a7fd633f678866d4
Source dataset
uspto-grants-2012_11
Patent number
US08318928B2

Reaction notes

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