Triethylamine → Ethyl 6-trimethylsilylethynyl-1,2-dihydro-2-(trifluoromethyl)-3-quinolinecarboxylate

HRID 650198

反応式

HRID 650198 の反応式
I[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[NH:8][CH:7]([C:12]([F:15])([F:14])[F:13])[C:6]([C:16]([O:18][CH2:19][CH3:20])=[O:17])=[CH:5]2.[CH3:21][Si:22]([C:25]#[CH:26])([CH3:24])[CH3:23].C(N(CC)CC)C.C(OCC)(=O)C>C(#N)C.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cu]I>[CH3:21][Si:22]([C:25]#[C:26][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[NH:8][CH:7]([C:12]([F:15])([F:14])[F:13])[C:6]([C:16]([O:18][CH2:19][CH3:20])=[O:17])=[CH:5]2)([CH3:24])[CH3:23]

参加物

8

反応物 4

HCID 8471TriethylamineHCID 8857Ethyl AcetateHCID 66111TrimethylsilylacetyleneHCID 21883508Ethyl 6-iodo-1,2-dihydro-2-(trifluoromethyl)-3-quinolinecarboxylate

生成物 1

HCID 21883639Ethyl 6-trimethylsilylethynyl-1,2-dihydro-2-(trifluoromethyl)-3-quinolinecarboxylate収率 38.4%

試薬・触媒・溶媒 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)触媒HCID 178418476HCID 178418476、化合物触媒HCID 6342Acetonitrile溶媒

実験手順

The ethyl 6-iodo-1,2-dihydro-2-(trifluoromethyl)-3-quinolinecarboxylate (Example 160, Step 1)(750 mg, 1.89 mmol), trimethylsilylacetylene (925 mg, 9.44 mmol), dichlorobis(triphenylphosphine)palladium(II) (35 mg, 0.05 mmol), copper(I)iodide (9.5 mg, 0.05 mmol), and triethylamine (953 mg, 9.44 mmol) were mixed at room temperature for 2 h in acetonitrile (10 mL). The resulting black heterogeneous mixture was poured into ethyl acetate(50 mL) and extracted with water (2×25 mL), 1 N aqueous hydrochloric acid (25 mL), and saturated aqueous ammonium chloride (2×25 mL). The organic layer was dried over sodium sulfate and solvent removed at reduce pressure. The product was purified by flash chromatography (0-25% ethyl acetate/hexanes, silica gel). A black semisolid was isolated which upon trituration with hexanes afforded ethyl 6-trimethylsilylethynyl-1,2-dihydro-2-(trifluoromethyl)-3-quinolinecarboxylate as a yellow solid(267 mg, 38%): mp 117-119° C. 1H NMR (CDCl3, 300 MHz) 7.65 (s, 1H), 7.24-7.32 (m, 2H), 6.55 (d, 1H, J=8.0 Hz), 5.08-5.18 (m, 1H), 4.66 (brs, 1H), 4.24-4.64 (m, 2H), 1.34 (t, 3H, J=7.1 Hz) 0.22 (s, 9H). ESHRMS m/z 368.1306 (Calc'd for M+H 368.1293).

後処理

  1. extractionextracted with water (2×25 mL), 1 N aqueous hydrochloric acid (25 mL), and saturated aqueous ammonium chloride (2×25 mL)
  2. dry with materialThe organic layer was dried over sodium sulfate and solvent
  3. customremoved
  4. customThe product was purified by flash chromatography (0-25% ethyl acetate/hexanes, silica gel)
  5. customA black semisolid was isolated which upon trituration with hexanes

出典と根拠

ORDレコード
ord-bbf91d6323c646aa822f679d8acf58cc
出典データセット
uspto-grants-2001_08
特許番号
US06271253B1

関連ノート

読み込み中…