Chlorotrimethylsilane → HCID 86666945, compound

HRID 511024Notes

Reaction equation

HRID 511024 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=O)C.[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 pt, 4.9 mmol) in DMF (54 mL). The mixture was heated at 70° C. for 10 min and then cooled to room temperature. Chlorotrimethylsilane (6204, 4.9 mmol) was added dropwise and stirring was continued for 1 hour. A solution of tert-butyl 3-iodoazetidine-1-carboxylate (17 g, 61 mmol) in DMF (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 DMF (120 mL) was added quickly. The reaction mixture was stirred overnight at room temperature. The reaction mixture was then partitioned between EtOAc 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 EtOAc 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 EtOAc 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-af0a0557527c4f24a34a4cd94fac2093
Source dataset
uspto-grants-2015_08
Patent number
US09096600B2

Reaction notes

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