Chlorotrimethylsilane → HCID 66592868, compound

HRID 1037614Notes

Reaction equation

HRID 1037614 reaction equation
C[Si](C)(C)Cl.BrCCBr.[C:10]([O:14][C:15]([N:17]1[CH2:22][CH2:21][CH:20](I)[CH2:19][CH2:18]1)=[O:16])([CH3:13])([CH3:12])[CH3:11].Cl[C:25]1[C:30]([NH2:31])=[CH:29][C:28]([Cl:32])=[CH:27][N:26]=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].O>[C:10]([O:14][C:15]([N:17]1[CH2:22][CH:21]=[C:20]([C:25]2[C:30]([NH2:31])=[CH:29][C:28]([Cl:32])=[CH:27][N:26]=2)[CH2:19][CH2:18]1)=[O:16])([CH3:13])([CH3:12])[CH3:11]

Participants

10

Reactant 4

HCID 6397ChlorotrimethylsilaneHCID 78391,2-DibromoethaneHCID 27999993-Amino-2,5-dichloropyridineHCID 10892302Tert-butyl 4-iodopiperidine-1-carboxylate

Product 1

HCID 66592868HCID 66592868, compoundYield 46.7%

Reagents, catalysts & solvents 5

HCID 23994ZincCatalystHCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 31374DimethylacetamideSolvent3×

Procedure

A mixture of trimethylchlorosilane and 1,2-dibromoethane (7:5 v/v, 0.125 ml) was added dropwise (keeping the T° C. below 50° C.) to a suspension of zinc powder (422 mg) in dimethylacetamide (3 ml). The mixture was stirred 20 min at room temperature then a solution of 1-(t-butoxycarbonyl)-4-iodo-piperidine (1.62 g, prepared in 2 steps from 1-(t-butoxycarbonyl)-piperidin-4-one according to J. Org. Chem. 2004, 5120) in dimethylacetamide (3 ml) was added dropwise over 5 min (slightly exothermic). The resulting mixture was stirred at room temperature for 30 min then cannulated into a mixture of 2,5-dichloro-3-aminopyridine (603 mg), copper(I) iodide (42 mg) and PdCl2(dppf) (91 mg) in dimethylacetamide (5 ml). The resulting mixture was stirred at 80° C. for 3 hours, cooled to room temperature, poured into water, extracted with ethyl acetate, dried over sodium sulfate and concentrated in vacuo. The residue was subjected to silica gel chromatography (ethyl acetate:cyclohexane 3:7) to afford 3-amino-5-chloro-3′,6′-dihydro-2′H-[2,4]bipyridinyl-1′-carboxylic acid tert-butyl ester (535 mg) as a yellow solid. 1H NMR (400 MHz, CDCl3) 1.4 (s, 9H), 1.8 (m, 4H), 2.6 (m, 1H), 2.8 (m, 2H), 3.7 (br s, 2H), 4.2 (m, 2H), 6.9 (s, 1H), 7.9 (s, 1H).

Workup

  1. additionwas added dropwise (
  2. stirringThe resulting mixture was stirred at room temperature for 30 min
  3. stirringThe resulting mixture was stirred at 80° C. for 3 hours
  4. temperaturecooled to room temperature
  5. extractionextracted with ethyl acetate
  6. dry with materialdried over sodium sulfate
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-47afc2db8437456e96f0af15b91b048d
Source dataset
uspto-grants-2013_10
Patent number
US08546569B2

Reaction notes

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