Chlorotrimethylsilane → HCID 90015386, compound

HRID 1778189Notes

Reaction equation

HRID 1778189 reaction equation
BrCCBr.C[Si](Cl)(C)C.[C:10]([O:14][C:15]([N:17]1[CH2:20][CH:19](I)[CH2:18]1)=[O:16])([CH3:13])([CH3:12])[CH3:11].[Cl:22][C:23]1[CH:28]=[C:27](I)[CH:26]=[C:25]([Cl:30])[N:24]=1>CN(C)C(=O)C.CCOC(C)=O.[Zn].C1C=CC(P([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.C1C=CC(P([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.Cl[Pd]Cl.[Fe].[Cu]I>[Cl:22][C:23]1[CH:28]=[C:27]([CH:19]2[CH2:20][N:17]([C:15]([O:14][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:16])[CH2:18]2)[CH:26]=[C:25]([Cl:30])[N:24]=1

Participants

10

Reactant 4

HCID 6397ChlorotrimethylsilaneHCID 78391,2-DibromoethaneHCID 11000522Tert-butyl 3-iodoazetidine-1-carboxylateHCID 117373932,6-Dichloro-4-iodopyridine

Product 1

HCID 90015386HCID 90015386, compoundYield 58.3%

Reagents, catalysts & solvents 5

HCID 23994ZincCatalystHCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178477754HCID 178477754, compoundCatalystHCID 8857Ethyl AcetateSolventHCID 31374DimethylacetamideSolvent2×

Procedure

Under a nitrogen atmosphere, zinc dust (6.91 g, 105 mmol) was suspended in N,N-dimethylacetamide (10 mL) and 1,2-dibromoethane (1.08 mL, 12.4 mmol) was added, followed by careful addition of trimethylsilylchloride (1.61 mL, 12.4 mmol) and was added cautiously over 5 min while the flask sat on a bed of ice. The bath was removed, and after stirring for a further 15 min, a solution of N-(tert-butoxycarbonyl)-3-iodoazetidine (25.1 g, 86.9 mmol) in N,N-dimethylacetamide (30 mL) was added over 30 min and stirring was continued for an additional 30 min. In the open atmosphere, this mixture was filtered through Celite as quickly as possible, rinsing with N,N-dimethylacetamide (100 mL). The resulting yellow solution was injected into a separately prepared, nitrogen flushed vessel containing [1,1-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (2.56 g, 3.10 mmol), copper(I) iodide (1.18 g, 6.21 mmol) and 2,6-dichloro-4-iodopyridine (17.0 g, 62.1 mmol) and this mixture was stirred at 80° C. for 19.5 h. After cooling to rt, the mixture was diluted with EtOAc and washed with water (3×). On the third time, filtration through Celite was necessary to break the emulsion, following which, the organics were washed with brine and then dried over MgSO4. After being freed of volatiles, the resultant residue was purified by flash column chromatography (100:0-70:30 heptanes/EtOAc) to afford tert-butyl 3-(2,6-dichloropyridin-4-yl)azetidine-1-carboxylate as a white solid (10.98 g, 58%); 1H NMR (400 MHz, CDCl3) δ 7.22 (s, 2H), 4.35 (dd, J=8.7, 5.6 Hz, 2H), 3.92 (dd, J=8.7, 5.6 Hz, 2H), 3.73-3.61 (m, 1H), 1.47 (s, 9H).

Workup

  1. additionwas added cautiously over 5 min while the flask
  2. customThe bath was removed
  3. stirringstirring
  4. waitwas continued for an additional 30 min
  5. filtrationIn the open atmosphere, this mixture was filtered through Celite as quickly as possible,
  6. washrinsing with N,N-dimethylacetamide (100 mL)
  7. customa separately prepared
  8. stirringthis mixture was stirred at 80° C. for 19.5 h
  9. washwashed with water (3×)
  10. filtrationOn the third time, filtration through Celite
  11. washthe organics were washed with brine
  12. dry with materialdried over MgSO4
  13. customthe resultant residue was purified by flash column chromatography (100:0-70:30 heptanes/EtOAc)

Sources & evidence

ORD record
ord-71cd8cc0e73e436e8a6156661e09d9bd
Source dataset
uspto-grants-2016_02
Patent number
US09266862B2

Reaction notes

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