Dimethylformamide → HCID 10570280, compound

HRID 1078706Notes

Reaction equation

HRID 1078706 reaction equation
[CH3:1][N:2](C)C=O.C(Cl)(=O)C(Cl)=O.[C:12]([O:16][C:17]([N:19]1[CH2:23][C@H:22]([O:24][Si:25]([C:28]([CH3:31])([CH3:30])[CH3:29])([CH3:27])[CH3:26])[CH2:21][C@H:20]1[CH2:32][OH:33])=[O:18])([CH3:15])([CH3:14])[CH3:13].C(N(CC)CC)C.C[Si](C#N)(C)C>C(Cl)Cl.C1C=CC=CC=1.CO>[C:12]([O:16][C:17]([N:19]1[CH2:23][C@H:22]([O:24][Si:25]([C:28]([CH3:31])([CH3:30])[CH3:29])([CH3:27])[CH3:26])[CH2:21][C@H:20]1[CH:32]([C:1]#[N:2])[OH:33])=[O:18])([CH3:15])([CH3:14])[CH3:13]

Participants

9

Reactant 5

HCID 6228DimethylformamideHCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 82115Trimethylsilyl cyanideHCID 11078078tert-butyl (2S,4R)-4-((tert-butyldimethylsilyl)oxy)-2-(hydroxymethyl)pyrrolidine-1-carboxylate

Product 1

HCID 10570280HCID 10570280, compoundYield 90.3%

Reagents, catalysts & solvents 3

HCID 241BenzeneSolventHCID 887MethanolSolventHCID 6344DichloromethaneSolvent2×

Procedure

To a solution of N,N-dimethylformamide (2.54 ml, 35.8 mmol) and methylene chloride (34.5 ml) was added oxalyl chloride (1.53 ml, 17.5 mmol) at -78° C., and the mixture was stirred for 15 min at the same temperature. To the mixture was added dropwise a solution of (2S,4R)-N-tert-butoxycarbonyl-4-tert-butyldimethylsiloxy-2-hydroxymetylpyrrolidine (3.92 g, 11.8 mmol) in methylene chloride (34.5 ml) over a 10 min period. After stirring for 30 min, triethylamine (8.27 ml, 59.3 mmol) was added to the mixture, and the mixture was allowed to warm to room temperature. After stirring for 15 min, the reaction mixture was washed with water, dried over anhydrous magnesium sulfate, and concentrated in vacuo to give an oily residue, which was dissolved in benzene (20 ml). To the solution was added trimethylsilylcyanide (1.75 ml, 13.1 mmol), and the mixture was stirred for 12 h at room temperature. To the mixture was added methanol (15 ml), and further stirred. The solvent was removed in vacuo. The resulting residue was subjected to silica gel column chromatography (hexane:ethyl acetate=5:1) to give (2S,4R)-N-tert-butoxycarbonyl-4-tert-butyldimethylsiloxy-2-(1-cyano-1-hydroxymethyl)pyrrolidine (3.8 g, yield: 88.1%).

Workup

  1. stirringAfter stirring for 30 min
  2. stirringAfter stirring for 15 min
  3. washthe reaction mixture was washed with water
  4. dry with materialdried over anhydrous magnesium sulfate
  5. concentrationconcentrated in vacuo
  6. customto give an oily residue, which
  7. stirringthe mixture was stirred for 12 h at room temperature
  8. customThe solvent was removed in vacuo

Sources & evidence

ORD record
ord-bc6e49f5f765405b812839eb4e2ec501
Source dataset
uspto-grants-1996_08
Patent number
US05550121

Reaction notes

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