Acetic Acid → methyl (3S,4R)-4-(2,4-difluorophenyl)-1-methylpyrrolidine-3-carboxylate

HRID 1992682Notes

Reaction equation

HRID 1992682 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C@@H:9]1[CH2:13][NH:12][CH2:11][C@H:10]1[C:14]([O:16][CH3:17])=[O:15].C=O.[C:20](O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCl>[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C@@H:9]1[CH2:13][N:12]([CH3:20])[CH2:11][C@H:10]1[C:14]([O:16][CH3:17])=[O:15]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 712FormaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 59130986methyl (3S,4R)-4-(2,4-difluorophenyl)pyrrolidine-3-carboxylate

Product 1

HCID 59130998methyl (3S,4R)-4-(2,4-difluorophenyl)-1-methylpyrrolidine-3-carboxylate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of methyl (3S,4R)-4-(2,4-difluorophenyl)pyrrolidine-3-carboxylate, from preparation 31 (500 mg, 2.07 mmol) and formaldehyde (155 μL, 2.07 mmol) in dichloromethane (20 mL) was added acetic acid (188 μL, 2.07 mmol) followed by sodium triacetoxyborohydride (659 mg, 3.11 mmol) at room temperature. The reaction mixture was stirred for 2 hours, diluted with dichloromethane (10 mL) and partitioned with saturated sodium hydrogen carbonate solution (40 mL). The phases were separated and the organic phase was washed with brine (20 mL), dried over magnesium sulfate, filtered and concentrated in vacuo to give the desired product as a colourless oil, 288 mg (54%).

Workup

  1. custompartitioned with saturated sodium hydrogen carbonate solution (40 mL)
  2. customThe phases were separated
  3. washthe organic phase was washed with brine (20 mL)
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-9e3ef630bd1a4254a695405cf4fc3078
Source dataset
uspto-grants-2010_01
Patent number
US07649002B2

Reaction notes

Loading…