Chlorotrimethylsilane → HCID 86666945, compound

HRID 1499887Notes

Reaction equation

HRID 1499887 reaction equation
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.[Cl:22][C:23]1[C:28]([Cl:29])=[CH:27][C:26]([C:30](=[O:32])[CH3:31])=[C:25]([O:33][CH3:34])[C:24]=1I>CN(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].O1C=CC=C1P(C1OC=CC=1)C1OC=CC=1>[C:30]([C:26]1[C:25]([O:33][CH3:34])=[C:24]([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:23]([Cl:22])=[C:28]([Cl:29])[CH:27]=1)(=[O:32])[CH3:31]

Participants

9

Reactant 4

HCID 6397ChlorotrimethylsilaneHCID 78391,2-DibromoethaneHCID 11000522Tert-butyl 3-iodoazetidine-1-carboxylateHCID 86666944HCID 86666944, compound

Product 1

HCID 86666945HCID 86666945, compoundYield 78.2%

Reagents, catalysts & solvents 4

HCID 23994ZincCatalystHCID 521585Tris(furan-2-yl)phosphaneCatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 6228DimethylformamideSolvent3×

Conditions

Temperature
70 °C

Procedure

Zinc (4.5 g, 69 mmol) was suspended with 1,2-dibromoethane (420 μL, 4.9 mmol) in N,N-dimethylformamide (54 mL). The mixture was heated at 70° C. for 10 min and then cooled to room temperature. Chlorotrimethylsilane (620 μL, 4.9 mmol) was added dropwise and stirring was continued for 1 h. A solution of tert-butyl 3-iodoazetidine-1-carboxylate (17 g, 61 mmol) in N,N-dimethylformamide (30 mL) was then added and the mixture was heated at 40° C. for 1 h before a mixture of 1-(4,5-dichloro-3-iodo-2-methoxyphenyl)ethanone (14 g, 41 mmol), tris(dibenzylideneacetone)dipalladium(0) (710 mg, 0.77 mmol) and tri-(2-furyl)phosphine (360 mg, 1.6 mmol) in N,N-dimethylformamide (120 mL) was added quickly. The reaction mixture was stirred overnight at room temperature. The reaction mixture was then partitioned between ethyl acetate and saturated ammonium chloride solution. The organic layer was washed with water, dried with magnesium sulfate, filtered, and concentrated to a crude residue that was purified by flash column chromatography using ethyl acetate in hexanes (0%-25%) to give the desired product (12 g, 77%). LCMS for C17H21Cl2NO4Na (M+Na)+: m/z=396.1; Found: 396.0.

Workup

  1. temperaturecooled to room temperature
  2. additionwas added quickly
  3. stirringThe reaction mixture was stirred overnight at room temperature
  4. customThe reaction mixture was then partitioned between ethyl acetate and saturated ammonium chloride solution
  5. washThe organic layer was washed with water
  6. dry with materialdried with magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated to a crude residue that
  9. customwas purified by flash column chromatography

Sources & evidence

ORD record
ord-9e0cff29986944f6b9333f4a62471fce
Source dataset
uspto-grants-2015_12
Patent number
US09199982B2

Reaction notes

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