Hydrochloric Acid → HCID 58968605、化合物

HRID 2075044ノート

反応式

HRID 2075044 の反応式
[F:1][C:2]([F:42])([F:41])[C:3]1[CH:4]=[C:5]([CH:34]=[C:35]([C:37]([F:40])([F:39])[F:38])[CH:36]=1)[CH2:6][N:7]([CH2:14][C:15]1[CH:20]=[C:19]([C:21]([F:24])([F:23])[F:22])[C:18]([CH3:25])=[CH:17][C:16]=1[C:26]([CH:28]1[CH2:33][CH2:32][CH2:31][CH2:30][CH2:29]1)=[O:27])[C:8]1[N:9]=[N:10][N:11]([CH3:13])[N:12]=1.[CH3:43][Mg]Br.Cl.C(OCC)(=O)C>C1COCC1>[F:42][C:2]([F:1])([F:41])[C:3]1[CH:4]=[C:5]([CH:34]=[C:35]([C:37]([F:38])([F:39])[F:40])[CH:36]=1)[CH2:6][N:7]([CH2:14][C:15]1[CH:20]=[C:19]([C:21]([F:24])([F:23])[F:22])[C:18]([CH3:25])=[CH:17][C:16]=1[C:26]([CH:28]1[CH2:33][CH2:32][CH2:31][CH2:30][CH2:29]1)([OH:27])[CH3:43])[C:8]1[N:9]=[N:10][N:11]([CH3:13])[N:12]=1

参加物

6

反応物 4

HCID 313Hydrochloric AcidHCID 8857Ethyl AcetateHCID 58968652HCID 58968652、化合物HCID 178418573HCID 178418573、化合物

生成物 1

HCID 58968605HCID 58968605、化合物収率 97.2%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

反応条件

温度
0 °C

実験手順

To a solution of (2-(((3,5-bis(trifluoromethyl)benzyl)(2-methyl-2H-tetrazol-5-yl)amino)methyl)-5-methyl-4-(trifluoromethyl)phenyl)(cyclohexyl)methanone (52 mg, 0.085 mmol) in anhydrous THF (10 mL) under nitrogen at 0° C. was added methylmagnesium bromide (3.0 M solution in THF, 25.6 mg, 0.114 mL, 0.342 mmol). The solution was stirred at 0° C. for 30 minutes, then warmed to room temperature and stirred for 1.5 hours. The solution was then poured into a mixture of 2 N hydrochloric acid (10 mL) and ethyl acetate (20 mL). The solution was stirred at room temperature for 10 minutes then the layers were separated and the aqueous layer was extracted with ethyl acetate (3×15 mL). The combined organics layer was dried with anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The crude product was purified by flash chromatography on a 4 g RediSep column (Teledyne Isco Inc., Lincoln Nebr.) (eluted with 1-50% ethyl acetate in heptane) to yield the title compound (97.2%). 1H NMR (400 MHz, CDCl3) δ 7.73 (s, 1H) 7.68 (s, 2H) 7.33 (s, 1H) 7.17 (s, 1H) 5.39 (d, J=16.17 Hz, 1H) 4.82 (d, J=15.76 Hz, 1H) 4.77(s, 2H) 4.15(s, 3H) 2.39 (s, 3H) 1.62 (m, 6H) 1.24 (s, 3H) 1.04 (m, 5H). LC-MS calc. 623.5, found 624.6 (M+H)

後処理

  1. temperaturewarmed to room temperature
  2. stirringstirred for 1.5 hours
  3. stirringThe solution was stirred at room temperature for 10 minutes
  4. customthe layers were separated
  5. extractionthe aqueous layer was extracted with ethyl acetate (3×15 mL)
  6. dry with materialThe combined organics layer was dried with anhydrous sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe crude product was purified by flash chromatography on a 4 g RediSep column (Teledyne Isco Inc., Lincoln Nebr.) (eluted with 1-50% ethyl acetate in heptane)

出典と根拠

ORDレコード
ord-201ae5e8d43f473c8e0d60b4abaa2b9f
出典データセット
uspto-grants-2011_04
特許番号
US07919506B2

反応ノート

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