Dimethyl Sulfoxide → HCID 21480593, compound

HRID 1721795Notes

Reaction equation

HRID 1721795 reaction equation
C(Cl)(=O)C(Cl)=O.CS(C)=O.[CH:11]1[C:24]2[C:23]3([CH2:26][N:27]4[CH2:32][CH2:31][C:30]([C:34]5[CH:35]=[N:36][CH:37]=[C:38]([CH2:40][OH:41])[CH:39]=5)([OH:33])[CH2:29][CH2:28]4)[CH2:25][CH:16]([C:17]4[C:22]3=[CH:21][CH:20]=[CH:19][CH:18]=4)[C:15]=2[CH:14]=[CH:13][CH:12]=1.C(N(CC)CC)C>C(Cl)Cl>[CH:11]1[C:24]2[C:23]3([CH2:26][N:27]4[CH2:28][CH2:29][C:30]([C:34]5[CH:35]=[N:36][CH:37]=[C:38]([CH:40]=[O:41])[CH:39]=5)([OH:33])[CH2:31][CH2:32]4)[CH2:25][CH:16]([C:17]4[C:22]3=[CH:21][CH:20]=[CH:19][CH:18]=4)[C:15]=2[CH:14]=[CH:13][CH:12]=1

Participants

6

Reactant 4

HCID 679Dimethyl Sulfoxide2×HCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 21480603HCID 21480603, compound

Product 1

HCID 21480593HCID 21480593, compoundYield 74.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
-78 °C

Procedure

To a cooled solution (-78° C.) of oxalyl chloride (0.597 mL, 6.84 mmol, 2 eq) in methylene chloride (15 mL) under nitrogen was added freshly distilled dimethylsulfoxide (0.971 mL, 13.68 mmol, 4 eq). After 10 min 1-(9,10-dihydro-9,10-methanoanthracen-9-ylmethyl)-4-(5-(hydroxymethyl)-3-pyridyl)piperidin-4-ol (described in example 70) (1.41 g, 3.42 mmol) was added as a dimethylsulfoxide solution (15 mL). The reaction was stirred at -78° C. for 1 h prior to the addition of triethylamine (3.81 mL, 27.4 mmol, 8 eq). The cooling bath was removed and the reaction warmed to room temperature over 2 h. Water (35 mL) was added to quench the reaction and the product extracted into methylene chloride (3×20 mL). Combined organic extracts were dried over anhydrous magnesium sulfate, filtered, and reduced to a white solid. The reaction product was purified by flash chromatography over silica gel (65 mL, eluent 10% hexane in ethyl acetate ramped to straight ethyl acetate) to yield 1.04 g (74%) of the title compound. TLC analysis (Rf 0.25, 10% hexane in ethyl acetate). MS (CI, CH4) m/z 411 (M+1,100), 439 (M+29,14), 393 (18), 260 (7), 219 (10), 206 (25), 169 (12).

Workup

  1. customThe cooling bath was removed
  2. temperaturethe reaction warmed to room temperature over 2 h
  3. additionWater (35 mL) was added
  4. customto quench
  5. customthe reaction
  6. extractionthe product extracted into methylene chloride (3×20 mL)
  7. dry with materialCombined organic extracts were dried over anhydrous magnesium sulfate
  8. filtrationfiltered
  9. customThe reaction product was purified by flash chromatography over silica gel (65 mL, eluent 10% hexane in ethyl acetate ramped to straight ethyl acetate)

Sources & evidence

ORD record
ord-7f56471f3d3c48188be0b87377acde7d
Source dataset
uspto-grants-1996_04
Patent number
US05512575

Reaction notes

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