Dimethyl Sulfoxide → tert-Butyl (2S,4R)-4-((tert-butyldimethylsilyl)oxy)-2-formylpyrrolidine-1-carboxylate

HRID 2359662Notes

Reaction equation

HRID 2359662 reaction equation
C(Cl)(=O)C(Cl)=O.CS(C)=O.[C:11]([O:15][C:16]([N:18]1[CH2:22][C@H:21]([O:23][Si:24]([C:27]([CH3:30])([CH3:29])[CH3:28])([CH3:26])[CH3:25])[CH2:20][C@H:19]1[CH2:31][OH:32])=[O:17])([CH3:14])([CH3:13])[CH3:12].CCN(CC)CC>C(Cl)Cl>[C:11]([O:15][C:16]([N:18]1[CH2:22][C@H:21]([O:23][Si:24]([C:27]([CH3:30])([CH3:29])[CH3:28])([CH3:26])[CH3:25])[CH2:20][C@H:19]1[CH:31]=[O:32])=[O:17])([CH3:14])([CH3:13])[CH3:12]

Participants

6

Reactant 4

HCID 679Dimethyl SulfoxideHCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 11078078tert-butyl (2S,4R)-4-((tert-butyldimethylsilyl)oxy)-2-(hydroxymethyl)pyrrolidine-1-carboxylate

Product 1

HCID 10969557tert-Butyl (2S,4R)-4-((tert-butyldimethylsilyl)oxy)-2-formylpyrrolidine-1-carboxylateYield 64%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of oxalyl chloride (0.16 mL; 1.785 mmol) in CH2Cl2 (2 mL) at −78° C. was added DMSO (0.25 mL; 3.55 mmol) dropwise and the mixture was stirred for 10 min. The mixture was then treated with a solution of Compound 27c (395 mg; 1.19 mmol) in CH2Cl2 (3 mL) dropwise and continually stirred for 20 min. To the resultant mixture was added Et3N (0.5 mL; 3.55 mmol) dropwise and the mixture was stirred at −78° C. for 30 min. The mixture was allowed to warm to ambient temperature while continually stirring over 20 min. The reaction mixture was quenched with saturated NH4Cl (aq), extracted with EtOAc, washed with water and brine; and the combined organic extracts were dried over Na2SO4, and concentrated under reduced pressure to give the crude material. The crude material was purified by flash column chromatography (SiO2), eluting with a heptane-EtOAc gradient to afford Compound 27d (250 mg; 64% yield). 1H-NMR (400 MHz, CDCl3): δ 9.44-9.57 (m, 1H), 4.20-4.39 (m, 1H), 3.35-3.57 (m, 1H), 1.89-2.09 (m, 1H), 1.44-1.49 (m, 9H), 0.88 (s, 9H), 0.08 (s, 6H); MS: m/z 330.2 (M+H)+.

Workup

  1. stirringcontinually stirred for 20 min
  2. stirringthe mixture was stirred at −78° C. for 30 min
  3. stirringwhile continually stirring over 20 min
  4. customThe reaction mixture was quenched with saturated NH4Cl (aq)
  5. extractionextracted with EtOAc
  6. washwashed with water and brine
  7. dry with materialand the combined organic extracts were dried over Na2SO4
  8. concentrationconcentrated under reduced pressure
  9. customto give the crude material
  10. customThe crude material was purified by flash column chromatography (SiO2)
  11. washeluting with a heptane-EtOAc gradient

Sources & evidence

ORD record
ord-14a38e3a81cf4d96964112b4fecd5945
Source dataset
uspto-grants-2014_04
Patent number
US08685990B2

Reaction notes

Loading…