Dimethyl Sulfide → Tert-butyl 4,4-difluoro-2-(hydroxymethyl)pyrrolidine-1-carboxylate

HRID 354434

Reaction equation

HRID 354434 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:15][C:14]([F:17])([F:16])[CH2:13][C@H:9]1[C:10](O)=[O:11])=[O:7])([CH3:4])([CH3:3])[CH3:2].CSC>C1COCC1>[C:1]([O:5][C:6]([N:8]1[CH2:15][C:14]([F:16])([F:17])[CH2:13][CH:9]1[CH2:10][OH:11])=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

4

Reactant 2

HCID 1068Dimethyl SulfideHCID 22977458(2S)-1-[(tert-butoxy)carbonyl]-4,4-difluoropyrrolidine-2-carboxylic acid

Product 1

HCID 22001352Tert-butyl 4,4-difluoro-2-(hydroxymethyl)pyrrolidine-1-carboxylateYield 75%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of N-(tert-butoxycarbonyl) 4,4-difluoroproline (3.00 g, 11.9 mmol) in THF (20 ml) was added BH3.DMS (1.1 ml, 11.9 mmol) at room temperature. The mixture was heated at reflux for 2 h. After cooling to room temperature, the mixture was concntrated in vacuo. The residue was quenched by the addition of H2O (100 ml) and extracted with CHCl3 (2×200 ml). The combined extracts were dried over MgSO4 and evaporated. The residue was chromatographed on silica gel with CHCl3-EtOAc (4:1) as eluent to give 1-(tert-butoxycarbonyl)-4,4-difluoro-2-pyrrolidinylmethanol (2.11 g, 75%) as a colorless oil. 1H-NMR (CDCl3) δ1.48 (s, 9 H), 2.04-2.55 (m, 2 H), 3.59-4.17 (m, 5 H).

Workup

  1. customat room temperature
  2. temperatureThe mixture was heated
  3. temperatureat reflux for 2 h
  4. customThe residue was quenched by the addition of H2O (100 ml)
  5. extractionextracted with CHCl3 (2×200 ml)
  6. dry with materialThe combined extracts were dried over MgSO4
  7. customevaporated
  8. customThe residue was chromatographed on silica gel with CHCl3-EtOAc (4:1) as eluent

Sources & evidence

ORD record
ord-9f77c9a8aa9348f6bc1a65f05cb78ba1
Source dataset
uspto-grants-2004_06
Patent number
US06756378B2

Linked notes

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