Acetic Acid → (+/-)-(3S,4R)-4-(4-chloro-3-fluorophenyl)-1-methylpyrrolidin-3-amine

HRID 596072Notes

Reaction equation

HRID 596072 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C@H:8]2[C@H:12]([N+:13]([O-])=O)[CH2:11][N:10]([CH3:16])[CH2:9]2)=[CH:4][C:3]=1[F:17].C(O)(=O)C>CO.[Zn]>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C@@H:8]2[CH2:9][N:10]([CH3:16])[CH2:11][C@H:12]2[NH2:13])=[CH:4][C:3]=1[F:17]

Participants

5

Reactant 2

HCID 176Acetic AcidHCID 118054567(+/-)-(3R,4S)-3-(4-chloro-3-fluorophenyl)-1-methyl-4-nitropyrrolidine

Product 1

HCID 68295195(+/-)-(3S,4R)-4-(4-chloro-3-fluorophenyl)-1-methylpyrrolidin-3-amineYield 40%

Reagents, catalysts & solvents 2

HCID 23994ZincCatalystHCID 887MethanolSolvent

Procedure

Zinc dust (5.76 g, 88 mmol) was added into a mixture of (+/−)-(3R,4S)-3-(4-chloro-3-fluorophenyl)-1-methyl-4-nitropyrrolidine (2.28 g, 8.81 mmol) in MeOH (29.4 mL) and acetic acid (30 mL, 524 mmol). The reaction mixture was stirred at room temperature for 5 h and filtered. Solvent was removed under vacuum. The residue was neutralized to pH 9, then extracted by IPA:CHCl3 (3:7). The organic was dried over Na2SO4, filtered and concentrated. The crude product was purified by flash chromatography (DCM/Methanol/NH3 90:9:1) to obtain (+/−)-(3S,4R)-4-(4-chloro-3-fluorophenyl)-1-methylpyrrolidin-3-amine in 40% yield. LCMS (m/z): 229.2 (MH+), 0.25 min.

Workup

  1. filtrationfiltered
  2. customSolvent was removed under vacuum
  3. extractionextracted by IPA:CHCl3 (3:7)
  4. dry with materialThe organic was dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude product was purified by flash chromatography (DCM/Methanol/NH3 90:9:1)

Sources & evidence

ORD record
ord-e21ca25ac30b42c283aa019d7b703ff8
Source dataset
uspto-grants-2016_01
Patent number
US09242996B2

Reaction notes

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