Dimethyl Sulfoxide → Tert-butyl 4,4-difluoro-2-formylpyrrolidine-1-carboxylate

HRID 354398Notes

Reaction equation

HRID 354398 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][C:11]([F:14])([F:13])[CH2:10][CH:9]1[CH2:15][OH:16])=[O:7])([CH3:4])([CH3:3])[CH3:2].CCN(CC)CC.CS(C)=O>C(Cl)Cl>[C:1]([O:5][C:6]([N:8]1[CH2:12][C:11]([F:13])([F:14])[CH2:10][CH:9]1[CH:15]=[O:16])=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 679Dimethyl SulfoxideHCID 8471TriethylamineHCID 22001352Tert-butyl 4,4-difluoro-2-(hydroxymethyl)pyrrolidine-1-carboxylate

Product 1

HCID 23511694Tert-butyl 4,4-difluoro-2-formylpyrrolidine-1-carboxylateYield 67%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirred mixture of 1-(tert-butoxycarbonyl)-4,4-difluoro-2-pyrrolidinylmethanol (2.11 g, 8.89 mmol), Et3N (6.2 ml, 44.5 mmol), DMSO (6.3 ml, 88.9 mmol) in CH2Cl2 (20 ml) was added SO3-pyridine (4.25 g, 26.7 mmol). After 3 h stirring, the mixture was concentrated in vacuo and diluted with Et2O (200 ml). The resulting mixture was washed with 1 N HCl (100 ml) and brine (100 ml), dried over MgSO4, and concentrated in vacuo. The residue was chromatographed on silica gel with hexane-EtOAc (4:1) as eluent to give 1-(tert-butoxycarbonyl)-4,4-difluoro-2-pyrrolidinecarbaldehyde (1.40 g, 67%) as a yellow oil. 1H-NMR (CDCl3) δ1.45-1.52 (m, 9 H), 2.49 (m, 2 H), 3.75-3.88 (m, 2 H), 4.29-4.42 (m, 1 H), 9.54 and 9.60 (s, each, total 1 H).

Workup

  1. concentrationthe mixture was concentrated in vacuo
  2. additiondiluted with Et2O (200 ml)
  3. washThe resulting mixture was washed with 1 N HCl (100 ml) and brine (100 ml)
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated in vacuo
  6. customThe residue was chromatographed on silica gel with hexane-EtOAc (4:1) as eluent

Sources & evidence

ORD record
ord-e5557662dca544ac8e5c4666f7854951
Source dataset
uspto-grants-2004_06
Patent number
US06756378B2

Reaction notes

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