Chlorotrimethylsilane → HCID 58547743, compound

HRID 2207853Notes

Reaction equation

HRID 2207853 reaction equation
C[Si](Cl)(C)C.BrCCBr.I[CH:11]1[CH2:16][CH2:15][N:14]([C:17]([O:19][CH2:20][C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)=[O:18])[CH2:13][CH2:12]1.Cl[C:28]1[C:37]([O:38][CH:39]2[CH2:42][N:41]([C:43]3[CH:52]=[CH:51][C:50]4[C:45](=[CH:46][CH:47]=[CH:48][CH:49]=4)[N:44]=3)[CH2:40]2)=[N:36][C:35]2[C:30](=[CH:31][CH:32]=[CH:33][CH:34]=2)[N:29]=1>CC(N(C)C)=O.[Zn].[Cu]I.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].ClCCl.C(OCC)(=O)C>[N:44]1[C:45]2[C:50](=[CH:49][CH:48]=[CH:47][CH:46]=2)[CH:51]=[CH:52][C:43]=1[N:41]1[CH2:40][CH:39]([O:38][C:37]2[C:28]([CH:11]3[CH2:16][CH2:15][N:14]([C:17]([O:19][CH2:20][C:21]4[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=4)=[O:18])[CH2:13][CH2:12]3)=[N:29][C:30]3[C:35]([N:36]=2)=[CH:34][CH:33]=[CH:32][CH:31]=3)[CH2:42]1

Participants

10

Reactant 4

HCID 6397ChlorotrimethylsilaneHCID 78391,2-DibromoethaneHCID 53249826Benzyl 4-iodopiperidine-1-carboxylateHCID 58547703HCID 58547703, compound

Product 1

HCID 58547743HCID 58547743, compoundYield 92%

Reagents, catalysts & solvents 5

HCID 23994ZincCatalystHCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418807HCID 178418807, compoundCatalystHCID 8857Ethyl AcetateSolventHCID 31374DimethylacetamideSolvent3×

Procedure

A premixed mixture of TMSCl and 1,2-dibromoethane (7:5, v/v, 0.80 mL total volume added) was added dropwise over 5 minutes to a suspension of zinc (1.62 g, 24.8 mmol) in DMA (12 mL) under argon atmosphere. The mixture was stirred for 15 minutes before benzyl 4-iodopiperidine-1-carboxylate (7.13 g, 20.67 mmol) was added dropwise over 15 minutes as a solution in DMA (6 mL). This mixture was stirred for an additional 15 min before it was added slowly to a suspension of 2-chloro-3-((1-(quinolin-2-yl)azetidin-3-yl)oxy)quinoxaline (see PREPARATION P2.8; 5.0 g, 13.8 mmol), copper(I) iodide (0.26 g, 1.38 mmol), and Pd(dppf)Cl2 dichloromethane adduct (0.56 g, 0.69 mmol) in DMA (15 mL) under argon. This mixture was stirred at 80° C. for 2 hours, then cooled to room temperature. Ethyl acetate was added and the suspension was filtered through CELITE® to remove insoluble material. The filtrate was diluted with more ethyl acetate and then washed with water (3×), brine(1×), dried (MgSO4), filtered, and concentrated in vacuo to give an oil. This oil was purified by silica gel chromatography (0 to 100% EtOAc/hexane gradient) to give benzyl 4-(3-((1-(quinolin-2-yl)azetidin-3-yl)oxy)quinoxalin-2-yl)piperidine-1-carboxylate as an off-white solid (6.93 g, 92% yield).

Workup

  1. additionv/v, 0.80 mL total volume added)
  2. stirringThis mixture was stirred at 80° C. for 2 hours
  3. filtrationthe suspension was filtered through CELITE®
  4. customto remove insoluble material
  5. additionThe filtrate was diluted with more ethyl acetate
  6. washwashed with water (3×), brine(1×)
  7. dry with materialdried (MgSO4)
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customto give an oil
  11. customThis oil was purified by silica gel chromatography (0 to 100% EtOAc/hexane gradient)

Sources & evidence

ORD record
ord-b6c6985e1a8540638373b9a0d5025b60
Source dataset
uspto-grants-2016_06
Patent number
US09376450B2

Reaction notes

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