Aluminium lithium hydride → (R)-3-((1-Methylpyrrolidin-2-yl)methyl)-5-vinyl-1H-indole

HRID 610057ノート

反応式

HRID 610057 の反応式
[H-].[H-].[H-].[H-].[Li+].[Al+3].[CH:7]([C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[NH:14][CH:13]=[C:12]2[C:18]([C@H:20]1[CH2:24][CH2:23][CH2:22][N:21]1[C:25](OCC1C=CC=CC=1)=O)=O)=[CH2:8]>C1COCC1>[CH:7]([C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[NH:14][CH:13]=[C:12]2[CH2:18][C@H:20]1[CH2:24][CH2:23][CH2:22][N:21]1[CH3:25])=[CH2:8]

参加物

4

反応物 2

HCID 21226445Aluminium lithium hydrideHCID 54294345(R)-5-vinyl-3-[(N-carbobenzyloxypyrrolidin-2-yl) carbonyl]-1H-indole

生成物 1

HCID 10220397(R)-3-((1-Methylpyrrolidin-2-yl)methyl)-5-vinyl-1H-indole収率 71%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

実験手順

A solution (R)-3-(N-Benzyloxycarbonylpyrrolidin-2-ylcarbonyl )-5-bromo-1H-indole (Example 5a, 252 mg, 0.59 mmol), tributyl(vinyl)tin (0.20 mL, 0.68 mmol) and tetrakistriphenyphosphine palladium (0) (84 mg, 0.073 mmol) in anhydrous DMF (3 mL) was stirred at 95-100° C. for 1 day. After cooling to room temperature, the product was taken into ethyl acetate, filtered through celite, washed with water (2×) and brine (1×), dried over sodium sulfate and the solvent was removed in vacuo. Flash chromatography on silica gel (60-100% ethyl acetate in hexanes) yielded (R)-5-vinyl-3-[(N-carbobenzyloxypyrrolidin-2-yl)carbonyl]-1H-indole (115 mg, 52%). A solution of LAH (0.77 mL, 1M in THF, 0.77 mmol) was added slowly to a cooled (0° C.) solution of (R)-5-vinyl-3-[(N-carbobenzyloxypyrrolidin-2-yl) carbonyl]-1H-indole (115 mg, 0.31 mmol) in THF (5 mL). Once the addition was completed, the reaction mixture was stirred at reflux for 2 h prior to quenching with sodium sulfate decahydrate. The product was taken into ethyl acetate, filtered to remove the solid residue, and the solvent was removed in vacuo. Flash chromatography on silica gel (5% 2M methanolic ammonia in dichloromethane) yielded (R)-5-vinyl-3-[(N-methylpyrrolidin-2-yl) methyl]-1H-indole (52 mg, 71%). HRMS-FAB+ for C16H20N2 : calculated MH+ :241.17047; found MH+ :241.17036.

後処理

  1. additionOnce the addition
  2. temperatureat reflux for 2 h
  3. customto quenching with sodium sulfate decahydrate
  4. filtrationfiltered
  5. customto remove the solid residue
  6. customthe solvent was removed in vacuo

出典と根拠

ORDレコード
ord-2e7702dd233c47179838b3856761ec9c
出典データセット
uspto-grants-1999_12
特許番号
US05998462

反応ノート

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