Trifluoroacetic acid → Methyl(3S,4R)-1-benzyl-4-(2,4-difluorophenyl)pyrrolidine-3-carboxylate

HRID 1992667Notes

Reaction equation

HRID 1992667 reaction equation
F[C:2](F)(F)C(O)=O.[CH2:8]([N:15]([Si](C)(C)C)[CH2:16]OC)[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1.[F:23][C:24]1[CH:29]=[C:28]([F:30])[CH:27]=[CH:26][C:25]=1/[CH:31]=[CH:32]/[C:33]([O:35][CH3:36])=[O:34]>ClCCl>[CH2:8]([N:15]1[CH2:16][C@@H:31]([C:25]2[CH:26]=[CH:27][C:28]([F:30])=[CH:29][C:24]=2[F:23])[C@H:32]([C:33]([O:35][CH3:36])=[O:34])[CH2:2]1)[C:9]1[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=1

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 15276473Methyl 3-(2,4-difluorophenyl)acrylateHCID 23062047Benzyl-methoxymethyl-trimethylsilanyl-amine

Product 1

HCID 59131001Methyl(3S,4R)-1-benzyl-4-(2,4-difluorophenyl)pyrrolidine-3-carboxylateYield 71%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A solution of trifluoroacetic acid (2.42 mL, 31.5 mmol) in dichloromethane (5 mL) was added at 0-5° C. to a stirred solution of N-benzyl-N-(methoxymethyl)trimethylsilylamine (45.1 g, 190 mmol) and methyl (2E)-3-(2,4-difluorophenyl)acrylate (from preparation 3) (25.1 g, 126 mmol) in dichloromethane (100 mL). After stirring overnight at room temperature, the organic solution was washed with saturated sodium bicarbonate solution and then brine. The resulting organic solution was dried over anhydrous sodium sulfate, filtered and then evaporated. The residue was purified by flash chromatography on silica gel eluting with toluene:tetrahydrofuran mixture (11:1) to afford the title compound (31.6 mL, 71%) as a colourless oil.

Workup

  1. washthe organic solution was washed with saturated sodium bicarbonate solution
  2. dry with materialThe resulting organic solution was dried over anhydrous sodium sulfate
  3. filtrationfiltered
  4. customevaporated
  5. customThe residue was purified by flash chromatography on silica gel eluting with toluene

Sources & evidence

ORD record
ord-a0728063d8db435d863b4c133a20ecfa
Source dataset
uspto-grants-2010_01
Patent number
US07649002B2

Reaction notes

Loading…