Dibromodifluoromethane → 4-(2,2-Difluoro-vinyl)-1-(4-methoxy-benzyl)-pyrrolidin-2-one

HRID 1295797Notes

Reaction equation

HRID 1295797 reaction equation
P(N(C)C)(N(C)C)N(C)C.[C:11](Br)(Br)([F:13])[F:12].[CH3:16][O:17][C:18]1[CH:32]=[CH:31][C:21]([CH2:22][N:23]2[C:27](=[O:28])[CH2:26][CH:25]([CH:29]=O)[CH2:24]2)=[CH:20][CH:19]=1.[PH4+]>C1COCC1>[F:12][C:11]([F:13])=[CH:29][CH:25]1[CH2:24][N:23]([CH2:22][C:21]2[CH:31]=[CH:32][C:18]([O:17][CH3:16])=[CH:19][CH:20]=2)[C:27](=[O:28])[CH2:26]1

Participants

6

Reactant 4

HCID 6382DibromodifluoromethaneHCID 15355Hexamethylphosphorous triamideHCID 5460504PhosphoniumHCID 589112571-(4-Methoxybenzyl)-5-oxopyrrolidine-3-carbaldehyde

Product 1

HCID 113001234-(2,2-Difluoro-vinyl)-1-(4-methoxy-benzyl)-pyrrolidin-2-oneYield 58%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

In a three necked flask under argon, (Me2N)3P (11.53 ml, 0.063 mol) is added to a solution of CF2Br2 (6.6 g, 0.031 mol) in THF (30 ml) at −78° C. (appearance of a white precipitate) and warmed to room temperature. A solution of the 1-(4-methoxy-benzyl)-5-oxo-pyrrolidine-3-carbaldehyde a3 (3.7 g, 0.016 mol) in THF (30 ml) is added dropwise to the pre-formed phosphonium salt. After 1 h, the reaction mixture is filtered through celite and concentrated in vacuo. The reaction mixture is diluted with hexane, washed with brine, dried over MgSO4 and concentrated in vacuo to afford the crude olefin which is purified by column chromatography on silicagel (CH2Cl2/MeOH: 99/01 (v/v)) to afford 2.45 g of the difluorovinyl derivative a4 (58%).

Workup

  1. filtrationthe reaction mixture is filtered through celite and
  2. concentrationconcentrated in vacuo
  3. additionThe reaction mixture is diluted with hexane
  4. washwashed with brine
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated in vacuo
  7. customto afford the crude olefin which
  8. customis purified by column chromatography on silicagel (CH2Cl2/MeOH: 99/01 (v/v))

Sources & evidence

ORD record
ord-84b361d78c8348b2b873d10e1c70ab2e
Source dataset
uspto-grants-2007_07
Patent number
US07244747B2

Reaction notes

Loading…