1-tert-butyl 2-methyl (2S)-4-methylidenepyrrolidine-1,2-dicarboxylate → 5-Azaspiro[2.4]heptane-5,6-dicarboxylic acid, 1,1-dibroMo-, 5-(1,1-diMethylethyl) 6-Methyl ester, (6S)-

HRID 1424669ノート

反応式

HRID 1424669 の反応式
[CH2:1]=[C:2]1[CH2:6][N:5]([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[C@H:4]([C:14]([O:16][CH3:17])=[O:15])[CH2:3]1.[Br:18][C:19](Br)([Br:23])C([O-])=O.[Na+]>[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.ClCCCl>[Br:18][C:19]1([Br:23])[C:2]2([CH2:3][C@@H:4]([C:14]([O:16][CH3:17])=[O:15])[N:5]([C:7]([O:9][C:10]([CH3:13])([CH3:11])[CH3:12])=[O:8])[CH2:6]2)[CH2:1]1

参加物

5

反応物 2

HCID 157359851-tert-butyl 2-methyl (2S)-4-methylidenepyrrolidine-1,2-dicarboxylateHCID 23677969Sodium tribromoacetate2 回

生成物 1

HCID 710145515-Azaspiro[2.4]heptane-5,6-dicarboxylic acid, 1,1-dibroMo-, 5-(1,1-diMethylethyl) 6-Methyl ester, (6S)-収率 88.4%

試薬・触媒・溶媒 2

HCID 74236Tetrabutylammonium Bromide触媒HCID 111,2-Dichloroethane溶媒

反応条件

温度
70 °C

実験手順

To a mixture of (S)-1-tert-butyl 2-methyl 4-methylenepyrrolidine-1,2-dicarboxylate (6 g, 24.9 mmol) and tetrabutylammonium bromide (161 mg, 0.02 eq) in anhydrous 1,2-dichloroethane (60 mL, 10 volumes) was added sodium tribromoacetate (17.48 g, 2.2 eq). The mixture was degassed and filled with N2 gas. It was heated at 70° C. for 2.5 hrs before additional sodium tribromoacetate (2.4 g, 0.3 eq) was added. The mixture was heated at 70° C. for 40 min. After the completion of the reaction, it was allowed to cool to room temperature and evaporated. The residue was diluted with 30% hexanes in tert-butyl methyl ether (100 mL) and filtered through a pad of celite. The filtrate was washed with water and brine, dried (Na2SO4), filtered and evaporated to dryness. The residue was passed through a silica gel (5.5 wt. volumes) pad with 0-15% tert-butyl methyl ether in hexanes and concentrated to afford the title compound (9.09 g, 88%) as a yellow oil as a mixture of two regioisomers. 1H NMR (500 MHz, CDCl3): 4.63-4.44 (m, 1H), 3.92-3.86 (m, 1H), 3.79 and 3.74 (2 s, 3H), 3.53-3.42 (m, 1H), 2.83-2.35 (m, 1.5H), 1.91-1.70 (m, 2.5H), 1.48 and 1.43 (2 s, 9H). ESI MS m/z (M+H)+ 413.85.

後処理

  1. customThe mixture was degassed
  2. additionfilled with N2 gas
  3. additionwas added
  4. customAfter the completion of the reaction, it
  5. temperatureto cool to room temperature
  6. customevaporated
  7. additionThe residue was diluted with 30% hexanes in tert-butyl methyl ether (100 mL)
  8. filtrationfiltered through a pad of celite
  9. washThe filtrate was washed with water and brine
  10. dry with materialdried (Na2SO4)
  11. filtrationfiltered
  12. customevaporated to dryness
  13. concentrationconcentrated

出典と根拠

ORDレコード
ord-6c69c92bcf1542d599f391c0d4c7cd3b
出典データセット
uspto-grants-2015_01
特許番号
US08927739B2

反応ノート

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