Dimethyl Sulfoxide → 1-Benzyl-3-(SR)-(4-oxopiperidin-1-ylmethyl)-4-(SR)-phenylpyrrolidine

HRID 1276492Notes

Reaction equation

HRID 1276492 reaction equation
C(Cl)(=O)C(Cl)=O.CS(C)=O.[CH2:11]([N:18]1[CH2:22][CH:21]([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[CH:20]([CH2:29][N:30]2[CH2:35][CH2:34][CH:33]([OH:36])[CH2:32][CH2:31]2)[CH2:19]1)[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1>C(Cl)Cl>[CH2:11]([N:18]1[CH2:22][CH:21]([C:23]2[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=2)[CH:20]([CH2:29][N:30]2[CH2:35][CH2:34][C:33](=[O:36])[CH2:32][CH2:31]2)[CH2:19]1)[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1

Participants

5

Reactant 3

HCID 679Dimethyl SulfoxideHCID 65578Oxalyl chlorideHCID 702003791-Benzyl-3-(SR)-(4-hydroxypiperidin-1-ylmethyl)-4-(SR)-phenyl-pyrrolidine

Product 1

HCID 702728111-Benzyl-3-(SR)-(4-oxopiperidin-1-ylmethyl)-4-(SR)-phenylpyrrolidineYield 95.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 0.14 mL of oxalylchloride in 3 mL of CH2CI2 at -70° C. was added 0.16 mL of DMSO. After 5 min 270 mg of 1-Benzyl-3-(SR)-(4-hydroxypiperidin- 1-ylmethyl)-4-(SR)-phenylpyrrolidine (from Example 14) in 3 mL of CH2Cl2 was added. After stirring for 10 min, the reaction was warmed to 0 OC for 45 min. The reaction was quenched with H20 and partitioned between 100 mL H20 and 100 mL CH2C-2. After separating phases, the aqueous layer was extracted with 100 mL CH2C-2. The combined organic layers were washed with 100 mL brine, dried over Na2SO4 and concentrated under vacuum. The residue was purified by flash chromatography eluting with 2% MeOH in CH2C12 to provide 256 mg of the title compound as a light yellow oil. RF : 0.40 (5% MeOH in CH2Cl2). 1H NMR (300 MHz, CDCl3): δ2.2-2.4 (m, 4H), 2.4-2.7 (m, 9H), 2.9-3.1 (m, 3H), 3.7 (ABq, 2H), 7.1-7.4 (m, 10H). Mass Spectrum (ESI): 349.3 (M+H).

Workup

  1. temperaturethe reaction was warmed to 0 OC for 45 min
  2. customThe reaction was quenched with H20
  3. custompartitioned between 100 mL H20 and 100 mL CH2C-2
  4. customAfter separating phases
  5. extractionthe aqueous layer was extracted with 100 mL CH2C-2
  6. washThe combined organic layers were washed with 100 mL brine
  7. dry with materialdried over Na2SO4
  8. concentrationconcentrated under vacuum
  9. customThe residue was purified by flash chromatography
  10. washeluting with 2% MeOH in CH2C12

Sources & evidence

ORD record
ord-9958d5965a8c42bd85bd70c2595e6d40
Source dataset
uspto-grants-2000_12
Patent number
US06166037

Reaction notes

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