Methyl iodide → HCID 13080739, compound

HRID 1943077Notes

Reaction equation

HRID 1943077 reaction equation
[Si:1]([O:8][CH2:9][C@H:10]1[C@H:14]([O:15][CH:16]2[CH2:21][CH2:20][CH2:19][CH2:18][O:17]2)[CH2:13][C@H:12]([OH:22])[C@@H:11]1[CH2:23]/[CH:24]=[CH:25]\[CH2:26][CH2:27][CH2:28][C:29]([OH:31])=[O:30])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[C:32]1(C2CCCCCCCCCC=2)CCCCCCCCNN=1.CI>C(#N)C>[Si:1]([O:8][CH2:9][C@H:10]1[C@H:14]([O:15][CH:16]2[CH2:21][CH2:20][CH2:19][CH2:18][O:17]2)[CH2:13][C@H:12]([OH:22])[C@@H:11]1[CH2:23]/[CH:24]=[CH:25]\[CH2:26][CH2:27][CH2:28][C:29]([O:31][CH3:32])=[O:30])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 6328Methyl iodide3×HCID 13080736HCID 13080736, compoundHCID 536302743-(Cycloundecen-1-yl)-1,2-diazacycloundec-2-ene3×

Product 1

HCID 13080739HCID 13080739, compoundYield 89.5%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A solution of (Z)-7-[(1R,2S,3R,5S)-2-(t-butyldimethylsilyloxymethyl)-5-hydroxy-3-(2-tetrahydropyranyloxy)cyclopentyl]-5-heptenoic acid (24) (261 mmol) in acetonitrile (1000 ml) was cooled on ice. Diazabicycloundecene (156.0 ml, 1044 mmol) was added thereto and methyl iodide (65.0 ml, 1044 mmol) was added drop wise to the solution. The reaction mixture was warmed to room temperature, and stirred for 14 hours. The reaction mixture was cooled on ice, diazabicycloundecene (39.0 ml, 261 mmol) and methyl iodide (16.3 ml, 261 mmol) were added, then, the mixture was stirred at room temperature for 1.25 hours. The reaction mixture was again cooled on ice, and diazabicycloundecene (39.0 ml, 261 mmol) and methyl iodide (16.3 ml, 261 mmol) were added. After stirring at room temperature for one hour, the reaction mixture was concentrated under reduced pressure. Ethyl acetate (400 ml) and water (400 ml) were added to the residue and the mixture was stirred, let to stand and then separated into two layers. The aqueous layer was extracted twice with ethyl acetate (400 ml), the organic layers were combined and sequentially washed with 1N-hydrochloric acid (600 ml), saturated sodium bicarbonate water (800 ml) and saturated aqueous sodium chloride (800 ml). After drying with anhydrous magnesium sulfate, the solution was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (Fuji Silysia BW-300: 2000 g; ethyl acetate:hexane=1:3), the fractions containing impurities were re-purified by silica gel column chromatography (Fuji Silysia BW-300: 190 g; ethyl acetate:hexane=1:3) to give methyl (Z)-7-[(1R,2S,3R,5S)-2-(t-butyldimethylsilyloxymethyl)-5-hydroxy-3-(2-tetrahydropyranyloxy)cyclopentyl]-5-heptenate (25) (110.4 g, 233.5 mmol, 89.5%) as colorless oil.

Workup

  1. additionwere added
  2. stirringthe mixture was stirred at room temperature for 1.25 hours
  3. additionwere added
  4. stirringAfter stirring at room temperature for one hour
  5. concentrationthe reaction mixture was concentrated under reduced pressure
  6. additionEthyl acetate (400 ml) and water (400 ml) were added to the residue
  7. stirringthe mixture was stirred
  8. customseparated into two layers
  9. extractionThe aqueous layer was extracted twice with ethyl acetate (400 ml)
  10. washsequentially washed with 1N-hydrochloric acid (600 ml), saturated sodium bicarbonate water (800 ml) and saturated aqueous sodium chloride (800 ml)
  11. dry with materialAfter drying with anhydrous magnesium sulfate
  12. concentrationthe solution was concentrated under reduced pressure
  13. customThe residue was purified by silica gel column chromatography (Fuji Silysia BW-300: 2000 g; ethyl acetate:hexane=1:3)
  14. additionthe fractions containing impurities
  15. customwere re-purified by silica gel column chromatography (Fuji Silysia BW-300: 190 g; ethyl acetate:hexane=1:3)

Sources & evidence

ORD record
ord-0cbe4fa0364a47dc8ddeb6449a22c14f
Source dataset
uspto-grants-2013_03
Patent number
US08389748B2

Reaction notes

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