Dimethyl Sulfoxide → 4-(4-Methoxyphenyl)-1-(1-(4-methylbenzyl)-2-oxopyrrolidin-3-yl)piperidin-3-one

HRID 1507244Notes

Reaction equation

HRID 1507244 reaction equation
CS(C)=O.C(Cl)(=O)C(Cl)=O.[OH:11][C@@H:12]1[C@@H:17]([C:18]2[CH:23]=[CH:22][C:21]([O:24][CH3:25])=[CH:20][CH:19]=2)[CH2:16][CH2:15][N:14]([CH:26]2[CH2:30][CH2:29][N:28]([CH2:31][C:32]3[CH:37]=[CH:36][C:35]([CH3:38])=[CH:34][CH:33]=3)[C:27]2=[O:39])[CH2:13]1.C(N(CC)CC)C>C(Cl)Cl>[CH3:25][O:24][C:21]1[CH:22]=[CH:23][C:18]([CH:17]2[CH2:16][CH2:15][N:14]([CH:26]3[CH2:30][CH2:29][N:28]([CH2:31][C:32]4[CH:33]=[CH:34][C:35]([CH3:38])=[CH:36][CH:37]=4)[C:27]3=[O:39])[CH2:13][C:12]2=[O:11])=[CH:19][CH:20]=1

Participants

6

Reactant 4

HCID 679Dimethyl SulfoxideHCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 118207300(+/-)-rel-3-((3R,4R)-3-hydroxy-4-(4-methoxyphenyl)piperidin-1-yl)-1-(4-methylbenzyl)pyrrolidin-2-one

Product 1

HCID 1182075054-(4-Methoxyphenyl)-1-(1-(4-methylbenzyl)-2-oxopyrrolidin-3-yl)piperidin-3-oneYield 92.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
-78 °C

Procedure

A mixture of DMSO (0.17 mL, 2.46 mmol) and DCM (4 mL) was cooled to −78° C., and oxalyl chloride (0.2 mL, 2.3 mmol) was added dropwise over 2 min. Following the addition, the mixture was stirred at the same temperature for 10 min. To the reaction was then added dropwise (±)-rel-3-((3R,4R)-3-hydroxy-4-(4-methoxyphenyl)piperidin-1-yl)-1-(4-methylbenzyl)pyrrolidin-2-one (375 mg, 0.95 mmol, mixture of four diastereomers from step E) in DCM over 5 min. The mixture was stirred for 1 h, and then triethylamine (1 mL, 7.6 mmol) was added and the mixture was stirred for 15 min, slowly warmed to rt, and then extracted with 3×40 mL of DCM. The combined organic layers were washed with 50 mL of brine, dried over Na2SO4, filtered, and concentrated under vacuum to yield 345 mg of 4-(4-methoxyphenyl)-1-(1-(4-methylbenzyl)-2-oxopyrrolidin-3-yl)piperidin-3-one (as a mixture of 4 diastereomers), which was used directly in the next step. LCMS (method)) RT 1.12 min, m/z 393 (M+H+), 411 (M+H++18), 1.18 min, m/z 393 (M+H+).

Workup

  1. additionthe addition
  2. stirringThe mixture was stirred for 1 h
  3. stirringthe mixture was stirred for 15 min
  4. temperatureslowly warmed to rt
  5. extractionextracted with 3×40 mL of DCM
  6. washThe combined organic layers were washed with 50 mL of brine
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-b51858053148475fbb44f30e31740f80
Source dataset
uspto-grants-2015_12
Patent number
US09221796B2

Reaction notes

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