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

HRID 1882138ノート

反応式

HRID 1882138 の反応式
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

参加物

6

反応物 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

生成物 1

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

試薬・触媒・溶媒 1

HCID 260Hydrogen Bromide溶媒

反応条件

温度
60 °C

実験手順

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)+.

後処理

  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

出典と根拠

ORDレコード
ord-0e826e62c22e4d60a7fd633f678866d4
出典データセット
uspto-grants-2012_11
特許番号
US08318928B2

反応ノート

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