Dimethyl Sulfoxide → (S)-tert-butyl 3-formylpyrrolidine-1-carboxylate

HRID 2382985Notes

Reaction equation

HRID 2382985 reaction equation
C(Cl)(=O)C(Cl)=O.CS(C)=O.[OH:11][CH2:12][C@H:13]1[CH2:17][CH2:16][N:15]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:14]1.CCN(CC)CC.C([O-])(O)=O.[Na+]>C(Cl)Cl>[CH:12]([C@H:13]1[CH2:17][CH2:16][N:15]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:14]1)=[O:11]

Participants

7

Reactant 5

HCID 679Dimethyl SulfoxideHCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 516892Sodium BicarbonateHCID 1514341tert-butyl (3S)-3-(hydroxymethyl)pyrrolidine-1-carboxylate

Product 1

HCID 1514343(S)-tert-butyl 3-formylpyrrolidine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Procedure

To a solution of oxalyl chloride (22.17 g, 0.176 mol) in CH2Cl2 (200 mL) was added dropwise a solution of DMSO (20.59 g, 0.264 mol) in CH2Cl2 (50 mL) at −78° C. The mixture was stirred for 0.5 hrs at this temperature. A solution of (S)-tert-butyl 3-(hydroxymethyl)pyrrolidine-1-carboxylate (M6) (11.8 g, 58.7 mmol) in CH2Cl2 (50 mL) was added dropwise to the reaction mixture at −78° C. The mixture continued to stir for 1 hr at that temperature. Et3N (29.7 g, 0.294 mol) was added at −78° C. The resultant mixture was warmed to room temperature and stirred for 3 hrs. The mixture was poured into saturated aqueous NaHCO3 and shaken. The organic layer was separated, washed twice with water, dried and evaporated to give a residue, which was purified by column chromatography (P.E./EtOAc 5:1) to give (S)-tert-butyl 3-formylpyrrolidine-1-carboxylate (M7). 1H NMR (CDCl3, 300 MHz): δ 9.68 (d, J=1.8 Hz, 1H), 3.67-3.68 (m, 1H), 3.51-3.55 (m, 1H), 3.35-3.40 (m, 2H), 2.99-3.04 (m, 1H), 2.04-2.18 (m, 2H), 1.46 (s, 9H).

Workup

  1. stirringto stir for 1 hr at that temperature
  2. stirringstirred for 3 hrs
  3. stirringshaken
  4. customThe organic layer was separated
  5. washwashed twice with water
  6. customdried
  7. customevaporated
  8. customto give a residue, which
  9. customwas purified by column chromatography (P.E./EtOAc 5:1)

Sources & evidence

ORD record
ord-43780e1022214192958e679f5e18e920
Source dataset
uspto-grants-2012_09
Patent number
US08263605B2

Reaction notes

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