Sodium Iodide → HCID 66596155, compound

HRID 1092801Notes

Reaction equation

HRID 1092801 reaction equation
[C:1]([O:5][C:6]([N:8]([C@@H:15]([CH2:18][C:19]([N:21]([CH:31]1[CH2:33][CH2:32]1)[CH2:22][C:23]1[CH:28]=[CH:27][CH:26]=[C:25]([Cl:29])[C:24]=1[Cl:30])=[O:20])[CH2:16][OH:17])[CH2:9][CH2:10][C:11]([O:13][CH3:14])=[O:12])=[O:7])([CH3:4])([CH3:3])[CH3:2].C(N(C(C)C)CC)(C)C.[I-].[Na+].[CH3:45][O:46][CH2:47]Cl>COCCOC>[C:1]([O:5][C:6]([N:8]([C@@H:15]([CH2:18][C:19]([N:21]([CH:31]1[CH2:32][CH2:33]1)[CH2:22][C:23]1[CH:28]=[CH:27][CH:26]=[C:25]([Cl:29])[C:24]=1[Cl:30])=[O:20])[CH2:16][O:17][CH2:45][O:46][CH3:47])[CH2:9][CH2:10][C:11]([O:13][CH3:14])=[O:12])=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 4

HCID 5238Sodium IodideHCID 7864Chloromethyl Methyl EtherHCID 81531Diisopropylethylamine2×HCID 66593733HCID 66593733, compound

Product 1

HCID 66596155HCID 66596155, compoundYield 53.1%

Reagents, catalysts & solvents 1

HCID 80711,2-DimethoxyethaneSolvent

Procedure

Into a 250 mL round bottom flask was added 4D (12.42 g, 24.7 mmol) and DME (137 mL). Di-isopropylethylamine (DIEA) or Hunig's base (23.6 mL, 135.7 mmol, 5.5 eq) and sodium iodide (14.79 g, 98.7 mmol, 4.0 eq) was added to the solution and cooled with an ice bath. Methoxymethyl chloride (MOMCl) (10.7 mL, 127.1 mmol, 5.15 eq) was added slowly at 0° C. The reaction was allowed to warm to room temperature overnight. Solvent was removed under vacuum and the residue was portioned between water (150 mL) and ethyl acetate (100 mL). The organic layer was separated and the aqueous layer was extracted with ethyl acetate (2×100 mL). The organic layers were combined and washed once with brine (100 mL). The organic phase was dried over sodium sulfate and filtered. Solvent was removed under vacuum and the residue was purified by column chromatography (30% ethyl acetate/hexanes) to give 4E (7.18 g, 53%) as a viscous oil. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 0.87 (m, 4H) 1.46 (br. s., 9H) 2.63 (br. s., 4H) 3.36 (s, 3H) 3.66 (s, 8H) 4.06-4.30 (m, 1H) 4.62 (m, 3H) 4.79 (m, 1H) 6.94 (d, J=7.83 Hz, 1H) 7.11-7.17 (m, 1H) 7.36 (dd, J=8.08, 1.26 Hz, 1H). ESI-MS:m/z 547.4 (M+H)+.

Workup

  1. temperaturecooled with an ice bath
  2. customSolvent was removed under vacuum
  3. customThe organic layer was separated
  4. extractionthe aqueous layer was extracted with ethyl acetate (2×100 mL)
  5. washwashed once with brine (100 mL)
  6. dry with materialThe organic phase was dried over sodium sulfate
  7. filtrationfiltered
  8. customSolvent was removed under vacuum
  9. customthe residue was purified by column chromatography (30% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-f68bb6246a924d6cb8de64e2f154baef
Source dataset
uspto-grants-2012_03
Patent number
US08129538B1

Reaction notes

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