Lithium Hexamethyldisilazide → 1-tert-butyl 4-ethyl 4-((3-iodo-1-isopropyl-1H-pyrazol-4-yl)methyl)piperidine-1,4-dicarboxylate

HRID 711029ノート

反応式

HRID 711029 の反応式
[N:1]1([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH2:6][CH2:5][CH:4]([C:7]([O:9][CH2:10][CH3:11])=[O:8])[CH2:3][CH2:2]1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+].Br[CH2:30][C:31]1[C:32]([I:39])=[N:33][N:34]([CH:36]([CH3:38])[CH3:37])[CH:35]=1>O1CCCC1>[I:39][C:32]1[C:31]([CH2:30][C:4]2([C:7]([O:9][CH2:10][CH3:11])=[O:8])[CH2:3][CH2:2][N:1]([C:12]([O:14][C:15]([CH3:17])([CH3:16])[CH3:18])=[O:13])[CH2:6][CH2:5]2)=[CH:35][N:34]([CH:36]([CH3:38])[CH3:37])[N:33]=1

参加物

5

反応物 3

HCID 2733832Lithium HexamethyldisilazideHCID 27588121-Tert-butyl 4-ethyl piperidine-1,4-dicarboxylateHCID 674917084-(bromomethyl)-3-iodo-1-isopropyl-1H-pyrazole

生成物 1

HCID 674915631-tert-butyl 4-ethyl 4-((3-iodo-1-isopropyl-1H-pyrazol-4-yl)methyl)piperidine-1,4-dicarboxylate収率 78.3%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒2 回

反応条件

温度
-78 °C

実験手順

A solution of 1-tert-butyl 4-ethyl piperidine-1,4-dicarboxylate (0.54 mL, 2.11 mmol) in tetrahydrofuran (15 mL) in a dry 100 mL round bottom flask under nitrogen was cooled to −78° C. and then treated with lithium bis(trimethylsilyl) amide (1 M toluene, 2.13 mL, 2.13 mmol). After stirring for 45 minutes at −78° C., 4-(bromomethyl)-3-iodo-1-isopropyl-1H-pyrazole (535 mg, 1.63 mmol) was added as a suspension in 10 mL tetrahydrofuran. The mixture was stirred 1 hour at −78° C. and then allowed to stir 18 hours at room temperature. The reaction mixture was quenched with 20 mL saturated aqueous ammonium chloride, stirred 30 minutes at room temperature, diluted with 50 mL water and then extracted with ethyl acetate (2×50 mL). The combined organics were dried over sodium sulfate, filtered and concentrated. The residue was purified by flash chromatography (10-80% ethyl acetate/heptanes, 25 g silica gel) to yield 1-tert-butyl 4-ethyl 4-((3-iodo-1-isopropyl-1H-pyrazol-4-yl)methyl)piperidine-1,4-dicarboxylate (645 mg) as a clear oil. +ESI (M-tBu) 450.1; 1H NMR (400 MHz, CDCl3, δ): 7.02 (s, 3H), 4.44 (spt, J=6.6 Hz, 1H), 4.17 (m, 2H), 3.92 (m, 2H), 2.86 (m, 2H), 2.62 (s, 2H), 2.08 (m, 2H), 1.46 (m, 17H), 1.25 (t, J=7.1 Hz, 3H).

後処理

  1. stirringThe mixture was stirred 1 hour at −78° C.
  2. stirringto stir 18 hours at room temperature
  3. customThe reaction mixture was quenched with 20 mL saturated aqueous ammonium chloride
  4. stirringstirred 30 minutes at room temperature
  5. additiondiluted with 50 mL water
  6. extractionextracted with ethyl acetate (2×50 mL)
  7. dry with materialThe combined organics were dried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe residue was purified by flash chromatography (10-80% ethyl acetate/heptanes, 25 g silica gel)

出典と根拠

ORDレコード
ord-de4c053973094c9e9f24cf2f71a68d84
出典データセット
uspto-grants-2015_11
特許番号
US09181252B2

反応ノート

読み込み中…