Dimethyl Sulfoxide → Benzyl 4-formylbicyclo[2.2.2]octane-1-carboxylate

HRID 2105695Notes

Reaction equation

HRID 2105695 reaction equation
CS(C)=O.[CH2:5]([O:12][C:13]([C:15]12[CH2:22][CH2:21][C:18]([CH2:23][OH:24])([CH2:19][CH2:20]1)[CH2:17][CH2:16]2)=[O:14])[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1.C(C(CC)(CC)CN)C.C(N(CC)CC)C>C(Cl)Cl>[CH2:5]([O:12][C:13]([C:15]12[CH2:20][CH2:19][C:18]([CH:23]=[O:24])([CH2:21][CH2:22]1)[CH2:17][CH2:16]2)=[O:14])[C:6]1[CH:7]=[CH:8][CH:9]=[CH:10][CH:11]=1

Participants

6

Reactant 4

HCID 679Dimethyl SulfoxideHCID 8471TriethylamineHCID 15841159HCID 15841159, compoundHCID 865917484-Hydroxymethylbicyclo[2.2.2]octane-1-carboxylic acid benzyl ester

Product 1

HCID 86591749Benzyl 4-formylbicyclo[2.2.2]octane-1-carboxylate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Procedure

Oxalyl chloride (COCl)2 (16.5 ml, 188 mmol) in methylene chloride (150 ml) is cooled to −63°. DMSO (18 ml, 362 mmol) is then added dropwise. The resulting mixture is stirred for 30 minutes and then a mixture of 4-hydroxymethylbicyclo[2.2.2]octane-1-carboxylic acid benzyl ester (XVIII, Example 93, 34.5 g, 125 mmol) in methylene chloride (100 ml) is added over 15 minutes. After another 30 minutes, triethylethylamine (70 ml, 502 mmol) in methylene chloride (30 ml) is added over 25 minutes. (Extra Caution: extremely exothermic reaction when the first equivalent of the triethylamine is added.) The reaction mixture then stirred for another 45 minutes and the cooling bath is removed and allowed to warm up to 20-25°. Water (50 ml) is added and the organic layer is separated, dried over anhydrous sodium sulfate and concentrated to give the title compound, NMR (400 MHz, CDCl3) δ 9.51, 7.32, 5.11, 1.88 and 1.64.

Workup

  1. additionis added over 15 minutes
  2. waitAfter another 30 minutes
  3. additionis added
  4. stirring) The reaction mixture then stirred for another 45 minutes
  5. customthe cooling bath is removed
  6. temperatureto warm up to 20-25°
  7. additionWater (50 ml) is added
  8. customthe organic layer is separated
  9. dry with materialdried over anhydrous sodium sulfate
  10. concentrationconcentrated

Sources & evidence

ORD record
ord-1651a8e681a748ef8d585b5c44aee2d7
Source dataset
uspto-grants-2009_08
Patent number
US07579354B2

Reaction notes

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