Chlorotrimethylsilane → Tert-butyl 3-(4-bromo-2-methylphenyl)azetidine-1-carboxylate

HRID 340633ノート

反応式

HRID 340633 の反応式
BrCCBr.Cl[Si](C)(C)C.I[CH:11]1[CH2:14][N:13]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:12]1.O1C=CC=C1P(C1OC=CC=1)C1OC=CC=1.[Br:38][C:39]1[CH:40]=[CH:41][C:42](I)=[C:43]([CH3:45])[CH:44]=1>C1COCC1.[Zn].C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O>[Br:38][C:39]1[CH:40]=[CH:41][C:42]([CH:11]2[CH2:14][N:13]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:12]2)=[C:43]([CH3:45])[CH:44]=1

参加物

10

反応物 5

HCID 6397ChlorotrimethylsilaneHCID 78391,2-DibromoethaneHCID 521585Tris(furan-2-yl)phosphaneHCID 27246015-Bromo-2-iodotolueneHCID 11000522Tert-butyl 3-iodoazetidine-1-carboxylate

生成物 1

HCID 86692010Tert-butyl 3-(4-bromo-2-methylphenyl)azetidine-1-carboxylate

試薬・触媒・溶媒 4

HCID 23994Zinc触媒HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 962Water溶媒HCID 8028Tetrahydrofuran溶媒4 回

反応条件

温度
65 °C

実験手順

To a vial with zinc dust (2.77 g, 42.4 mmol) in anhydrous THF (15 mL) under nitrogen was added 1,2-dibromoethane (0.24 mL, 2.83 mmol), then the suspension was stirred at 65° C. for 3 min. After cooling to ambient temperature, chloro(trimethyl)silane (0.36 mL, 2.83 mmol) was added and the mixture was stirred at room temperature for 30 min. Then, a solution of tert-butyl 3-iodoazetidine-1-carboxylate (8.00 g, 28.3 mmol) in THF (10 mL) was added and the mixture was stirred for 45 min. P(2-furyl)3 (1.31 g, 5.7 mmol) and tris(dibenzylidene acetone)dipalladium (0) (2.59 g, 2.83 mmol) were added to a separate vial, dissolved in THF (5 mL) and stirred under nitrogen at ambient temperature for 10 min, then the mixture and 5-bromo-2-iodotoluene (4.84 mL, 33.9 mmol) in THF (10 mL) were added to the organozine reagent solution. The mixture was then placed in a 65° C. oil bath for 2 h. The reaction mixture was allowed to cool to room temperature and then was poured into water. The mixture was extracted with EtOAc, and the organic layer was concentrated in vacuo. Purification by chromatography on silica gel (0 to 50% EtOAc in hexanes, then 50 to 100% EtOAc in hexanes) provided the title compound: LCMS m/z 271.8 [M-t-Bu+2H]+; 1H NMR (500 MHz, acetone-d6) δ 7.40-7.30 (m, 3 H),4.23 (br, 2 H),3.99 (m, 1 H),3.91 (m, 2 H),2.21 (s, 3 H),1.42 (s, 9 H).

後処理

  1. temperatureAfter cooling to ambient temperature
  2. stirringthe mixture was stirred at room temperature for 30 min
  3. stirringthe mixture was stirred for 45 min
  4. stirringstirred under nitrogen at ambient temperature for 10 min
  5. customwas then placed in a 65° C.
  6. customfor 2 h
  7. temperatureto cool to room temperature
  8. extractionThe mixture was extracted with EtOAc
  9. concentrationthe organic layer was concentrated in vacuo
  10. customPurification by chromatography on silica gel (0 to 50% EtOAc in hexanes

出典と根拠

ORDレコード
ord-c614c8a216174400b1946f5985c42b9c
出典データセット
uspto-grants-2014_11
特許番号
US08895583B2

反応ノート

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