Iodine → HCID 10141268, compound

HRID 2181385Notes

Reaction equation

HRID 2181385 reaction equation
[Mg].II.Br[C:5]1[CH:10]=[CH:9][C:8]([O:11][CH3:12])=[CH:7][CH:6]=1.COCN[C:17](=[O:48])[CH2:18][CH2:19][CH2:20][CH2:21][O:22][C:23]1[CH:28]=[CH:27][C:26]([S:29]([C:32]2([C:38]([NH:40][O:41]C3CCCCO3)=[O:39])[CH2:37][CH2:36][O:35][CH2:34][CH2:33]2)(=[O:31])=[O:30])=[CH:25][CH:24]=1>O1CCCC1>[OH:41][NH:40][C:38]([C:32]1([S:29]([C:26]2[CH:27]=[CH:28][C:23]([O:22][CH2:21][CH2:20][CH2:19][CH2:18][C:17]([C:5]3[CH:10]=[CH:9][C:8]([O:11][CH3:12])=[CH:7][CH:6]=3)=[O:48])=[CH:24][CH:25]=2)(=[O:30])=[O:31])[CH2:33][CH2:34][O:35][CH2:36][CH2:37]1)=[O:39]

Participants

6

Reactant 4

HCID 807IodineHCID 77304-BromoanisoleHCID 5462224MagnesiumHCID 22484402HCID 22484402, compound

Product 1

HCID 10141268HCID 10141268, compoundYield 34.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

Part A. To a mixture of magnesium turnings (344 mg, 14.18 mmol) etched with iodine in anhydrous tetrahydrofuran (4 mL) at reflux was added 4-bromoanisole (1.2 mL, 9.45 mmol) dropwise over 10 min. The reaction mixture was heated at reflux for 45 min, and then cooled to ambient temperature. The prepared grignard reagent was added to a mixture of tetrahydro-4-[[4-[[5-(methoxymethylamino)-5-oxopentyl]oxy]phenyl]sulfonyl]-N-[(tetrahydro-2H-pyran-2-yl)oxy]-2H-pyran-4-carboxamide (1.0 g, 1.9 mmol, as prepared in Example 7) in anhydrous tetrahydrofuran (10 mL) at 0° C. The reaction mixture was warmed to ambient temperature and left stirring overnight. The reaction was quenched with saturated ammonium chloride, and then partitioned between ethyl acetate and water. The layers were separated, and the organic layer was washed with brine, dried over sodium sulfate, filtered, and concentrated in vacuo. The crude material was purified by flash chromatography using 50-100% ethyl acetate/hexanes to afford 320 mg (29%) of the desired ketone as a white powder. ESMS m/z=593 [M+NH4]+. HRMS calculated for C29H37NO9S: 593.2533 [M+NH4]+. found: 593.2555.

Workup

  1. temperatureat reflux
  2. temperatureThe reaction mixture was heated
  3. temperatureat reflux for 45 min
  4. temperatureThe reaction mixture was warmed to ambient temperature
  5. waitleft
  6. customThe reaction was quenched with saturated ammonium chloride
  7. custompartitioned between ethyl acetate and water
  8. customThe layers were separated
  9. washthe organic layer was washed with brine
  10. dry with materialdried over sodium sulfate
  11. filtrationfiltered
  12. concentrationconcentrated in vacuo
  13. customThe crude material was purified by flash chromatography

Sources & evidence

ORD record
ord-8bcc0dc15c004671ac1cf274292f17eb
Source dataset
uspto-grants-2005_05
Patent number
US06890928B2

Reaction notes

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