Chlorotrimethylsilane → Tert-butyl 4-(5-chloropyridin-2-yl)piperidine-1-carboxylate

HRID 32389

反応式

HRID 32389 の反応式
BrCCBr.C[Si](Cl)(C)C.I[CH:11]1[CH2:16][CH2:15][N:14]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:13][CH2:12]1.O1C=CC=C1P(C1OC=CC=1)C1OC=CC=1.Br[C:41]1[CH:46]=[CH:45][C:44]([Cl:47])=[CH:43][N:42]=1>C1COCC1.CC(N(C)C)=O.[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]>[Cl:47][C:44]1[CH:45]=[CH:46][C:41]([CH:11]2[CH2:16][CH2:15][N:14]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:13][CH2:12]2)=[N:42][CH:43]=1

参加物

10

反応物 5

HCID 6397ChlorotrimethylsilaneHCID 78391,2-DibromoethaneHCID 521585Tris(furan-2-yl)phosphaneHCID 8170982-Bromo-5-chloropyridineHCID 10892302Tert-butyl 4-iodopiperidine-1-carboxylate

生成物 1

HCID 66850771Tert-butyl 4-(5-chloropyridin-2-yl)piperidine-1-carboxylate収率 16%

試薬・触媒・溶媒 4

HCID 23994Zinc触媒HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 8028Tetrahydrofuran溶媒4 回HCID 31374Dimethylacetamide溶媒

反応条件

温度
65 °C

実験手順

Zn dust (225 mg, 3.5 mmol) was stirred in THF (1 mL) under Ar and 1,2-dibromoethane (50 μL) was added at room temperature. The mixture was heated to 65° C. for 3 min and allowed to cool to room temperature before trimethylsilyl chloride (70 μL) was added and the mixture was stirred at room temperature for 30 min. A solution of 4-iodo-N-Boc-piperidine (840 mg, 2.7 mmol) in THF (1.5 mL) was slowly added and the reaction mixture was stirred at 40° C. for 2 h. Pd2(dba)3 (22 mg, 0.024 mmol) and P(2-furyl)3 (23 mg, 0.10 mmol) were mixed in THF (0.5 mL), the mixture stirred at room temperature for 10 min and then added to the organozink reagent solution, followed by 2-bromo-5-chloro-pyridine (624 mg, 3.24 mmol) in THF (1 mL) and DMA (4 mL). The reaction mixture was heated at 80° C. for 3 h, allowed to cool to room temperature and then filtered through Celite and diluted with EtOAc. The filtrate was washed with saturated aqueous NaHCO3 and brine, dried Na2SO4 and concentrated. Purification on SiO2 eluting with heptane/EtOAc 95:5 to 2:1 gave tert-butyl 4-(5-chloropyridin-2-yl)piperidine-1-carboxylate as an yellow oil (128 mg, 16%). The oil was dissolved in THF (1.5 mL) and conc HCl (1.5 mL) and stirred at RT for 30 min. Concentration several times with toluene and EtOH gave the title compound (89 mg, 89%)

後処理

  1. additionwas added at room temperature
  2. additionwas added
  3. stirringthe reaction mixture was stirred at 40° C. for 2 h
  4. stirringthe mixture stirred at room temperature for 10 min
  5. additionadded to the organozink reagent solution
  6. temperatureThe reaction mixture was heated at 80° C. for 3 h
  7. temperatureto cool to room temperature
  8. filtrationfiltered through Celite
  9. additiondiluted with EtOAc
  10. washThe filtrate was washed with saturated aqueous NaHCO3 and brine, dried Na2SO4
  11. concentrationconcentrated
  12. customPurification on SiO2 eluting with heptane/EtOAc 95:5 to 2:1

出典と根拠

ORDレコード
ord-d4b8835e6e84467fb09105f63555bb07
出典データセット
uspto-grants-2008_09
特許番号
US07427631B2

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