Cesium carbonate → 1-(2-(Trimethylsilyl)ethanesulfonyl)-3-((3-methoxypropoxy)(2-(2-cyclohexylethyl)phenyl)methyl)piperidine

HRID 2355318

反応式

HRID 2355318 の反応式
[CH:1]([CH:3]1[CH2:8][CH2:7][CH2:6][CH2:5][CH2:4]1)=[CH2:2].C([O-])([O-])=O.[Cs+].[Cs+].[CH3:15][Si:16]([CH3:43])([CH3:42])[CH2:17][CH2:18][S:19]([N:22]1[CH2:27][CH2:26][CH2:25][CH:24]([CH:28]([O:36][CH2:37][CH2:38][CH2:39][O:40][CH3:41])[C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=2Br)[CH2:23]1)(=[O:21])=[O:20]>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].O1CCOCC1>[CH3:15][Si:16]([CH3:43])([CH3:42])[CH2:17][CH2:18][S:19]([N:22]1[CH2:27][CH2:26][CH2:25][CH:24]([CH:28]([O:36][CH2:37][CH2:38][CH2:39][O:40][CH3:41])[C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=2[CH2:2][CH2:1][CH:3]2[CH2:8][CH2:7][CH2:6][CH2:5][CH2:4]2)[CH2:23]1)(=[O:21])=[O:20]

参加物

6

反応物 3

HCID 10796Cesium carbonateHCID 12757VinylcyclohexaneHCID 59382843HCID 59382843、化合物

生成物 1

HCID 593829951-(2-(Trimethylsilyl)ethanesulfonyl)-3-((3-methoxypropoxy)(2-(2-cyclohexylethyl)phenyl)methyl)piperidine収率 82%

試薬・触媒・溶媒 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)触媒HCID 312751,4-Dioxane溶媒

実験手順

A sealed tube designed for a microwave reactor was filled with nitrogen and charged with vinylcyclohexane (66 mg, 0.595 mmol, 5.0 equiv) 9-BBN (0.5 M solution in THF, 1.07 mL, 4.5 equiv) and the clear solution was stirred overnight at rt. The flask was briefly opened and Cs2CO3 (213 mg, 0.119 mmol, 3.3 equiv), PdCl2(dppf) (11 mg, 0.119 mmol, 0.05 equiv), 1-(2-(trimethylsilyl)ethanesulfonyl)-3-((3-methoxypropoxy)(2-bromophenyl)methyl)-piperidine (100 mg, 0.197 mmol, 1.0 equiv), and dioxane (4 mL) added. The tube was degassed by three evacuate/N2 backfill cycles, then placed in a CEM microwave reactor and heated to 120° C. for 10 min. The solvent was removed and the product was extracted with EtOAc and filtered through a pad of Celite. The product was purified by flash chromatography on 12 g of silica, eluting with 0 to 27% EtOAc in hexanes, to afford 1-(2-(trimethylsilyl)ethanesulfonyl)-3-((3-methoxypropoxy)(2-(2-cyclohexylethyl)phenyl)methyl)piperidine (82%) as a mixture of diastereomers. 1H NMR (CDCl3) δ 0.02 (s, 9H), 0.8-1.9 (m, 24H), 2.5-2.8 (m, 4H), 3.3-4.4 (m, 11H), 7.1-7.3 (m, 4H). MS ESI+ve m/z 561 (M+Na+).

後処理

  1. customA sealed tube designed for a microwave reactor
  2. additionwas filled with nitrogen
  3. customThe tube was degassed by three
  4. customevacuate/N2 backfill cycles
  5. temperatureheated to 120° C. for 10 min
  6. customThe solvent was removed
  7. extractionthe product was extracted with EtOAc
  8. filtrationfiltered through a pad of Celite
  9. customThe product was purified by flash chromatography on 12 g of silica
  10. washeluting with 0 to 27% EtOAc in hexanes

出典と根拠

ORDレコード
ord-54aae341fb444bc4a170081577c607e0
出典データセット
uspto-grants-2010_07
特許番号
US07754737B2

関連ノート

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