Dimethyl Sulfoxide → HCID 14863946, compound

HRID 572031Notes

Reaction equation

HRID 572031 reaction equation
C(Cl)(=O)C(Cl)=O.CS(C)=O.[CH2:11]([O:18][C@H:19]1[CH2:23][N:22]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[C@H:21]([CH2:31][OH:32])[CH2:20]1)[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.C(N(CC)CC)C>ClCCl>[CH2:11]([O:18][C@H:19]1[CH2:23][N:22]([C:24]([O:26][C:27]([CH3:28])([CH3:29])[CH3:30])=[O:25])[C@H:21]([CH:31]=[O:32])[CH2:20]1)[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1

Participants

6

Reactant 4

HCID 679Dimethyl SulfoxideHCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 14821719HCID 14821719, compound

Product 1

HCID 14863946HCID 14863946, compoundYield 84%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
-78 °C

Procedure

To a stirred solution of oxalyl chloride (2.21 mL, 25.4 mmol) in dichloromethane (120 mL) at −78° C. was added dimethyl sulfoxide (3.6 mL, 50.8 mmol) dropwise via syringe. The mixture was stirred at −78° C. for 10 minutes, and a solution of tert-butyl (2S,4R)-4-(benzyloxy)-2-(hydroxymethyl)pyrrolidine-1-carboxylate (3.9 g, 12.69 mmol, Part A) in dichloromethane (30 mL) was added. The mixture was stirred at −78° C. for 15 minutes, and triethylamine (7.07 mL, 50.8 mol) was added. After 15 minutes, the reaction mixture was allowed to warm to 0° C. and stirred at that temperature for 30 minutes. The mixture was washed successively with water and brine, dried with MgSO4, filtered, and concentrated in vacuo. The crude product was purified by column chromatography on silica gel using a solvent gradient of 20-50% ethyl acetate in hexanes to give the title compound as a colorless oil (3.25 g, 84%). 1H NMR (400 MHz, pyridine-d5, 90° C.) δ ppm 9.62 (s, 1 H), 7.18-7.41 (m, 5 H), 4.37-4.56 (m, 3 H), 4.08-4.14 (m, 1 H), 3.88-3.74 (m, 1 H), 3.56 (dd, J=11.7, 4.7 Hz, 1 H) 2.19-2.29 (m, 1 H) 1.95-2.05 (m, 1 H) 1.45 (s, 9 H).

Workup

  1. stirringThe mixture was stirred at −78° C. for 15 minutes
  2. waitAfter 15 minutes
  3. temperatureto warm to 0° C.
  4. stirringstirred at that temperature for 30 minutes
  5. washThe mixture was washed successively with water and brine
  6. dry with materialdried with MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe crude product was purified by column chromatography on silica gel using a solvent gradient of 20-50% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-cad4cbfb722e4fffb8793aa793381a39
Source dataset
uspto-grants-2015_05
Patent number
US09029361B2

Reaction notes

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