Dimethyl Sulfoxide → (2S,4R)-4-(tert-butyl(dimethyl)silyl)oxy-1-methyl-pyrrolidine-2-carbaldehyde

HRID 2199339Notes

Reaction equation

HRID 2199339 reaction equation
CS(C)=O.C(Cl)(=O)C(Cl)=O.[Si:11]([O:18][C@H:19]1[CH2:23][N:22]([CH3:24])[C@H:21]([CH2:25][OH:26])[CH2:20]1)([C:14]([CH3:17])([CH3:16])[CH3:15])([CH3:13])[CH3:12].C(N(CC)CC)C>ClCCl>[Si:11]([O:18][C@H:19]1[CH2:23][N:22]([CH3:24])[C@H:21]([CH:25]=[O:26])[CH2:20]1)([C:14]([CH3:17])([CH3:16])[CH3:15])([CH3:13])[CH3:12]

Participants

6

Reactant 4

HCID 679Dimethyl SulfoxideHCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 68023406HCID 68023406, compound

Product 1

HCID 86667262(2S,4R)-4-(tert-butyl(dimethyl)silyl)oxy-1-methyl-pyrrolidine-2-carbaldehydeYield 109.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Procedure

Dimethyl sulfoxide (174 μL, 2.45 mmol) was dissolved in 20 mL of dichloromethane in a dry ice bath. After the system temperature was stable, oxalyl chloride (156 μL, 1.80 mmol) was added dropwise slowly. After stirring for 30 minutes, a solution of [(2S,4R)-4-(tert-butyl(dimethyl)silyl)oxy-1-methyl-pyrrolidin-2-yl]methanol 3d (300 mg, 1.20 mmol) in 2 mL of dichloromethane was added dropwise. After stirring for 45 minutes, the reaction mixture was added with triethylamine (510 μL, 3.67 mmol), and stirred for 10 minutes, then warmed up to room temperature and stirred for 1 hour. The reaction mixture was diluted with 100 mL of dichloromethane, washed with saturated sodium bicarbonate (20 mL), saturated ammonium chloride (20 mL) and saturated brine (20 mL) successively, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure to obtain the title compound (2S,4R)-4-(tert-butyl(dimethyl)silyl)oxy-1-methyl-pyrrolidine-2-carbaldehyde 3e (320 mg) crude product as a yellow oil, which was directly used in the next step.

Workup

  1. stirringAfter stirring for 45 minutes
  2. stirringstirred for 10 minutes
  3. stirringstirred for 1 hour
  4. washwashed with saturated sodium bicarbonate (20 mL), saturated ammonium chloride (20 mL) and saturated brine (20 mL) successively
  5. dry with materialdried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-1b57096667ad4152bb621bf05a5d71d1
Source dataset
uspto-grants-2016_06
Patent number
US09358227B2

Reaction notes

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