Tetrahydrofuran → trans-(+/-)-4-(4-Chloro-3-fluorophenoxy)-1-methylpyrrolidin-3-amine

HRID 2279605Notes

Reaction equation

HRID 2279605 reaction equation
[N:1]([C@H:4]1[C@H:8]([O:9][C:10]2[CH:15]=[CH:14][C:13]([Cl:16])=[C:12]([F:17])[CH:11]=2)[CH2:7][N:6]([CH3:18])[CH2:5]1)=[N+]=[N-].C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1COCC1>O>[Cl:16][C:13]1[CH:14]=[CH:15][C:10]([O:9][C@@H:8]2[CH2:7][N:6]([CH3:18])[CH2:5][C@H:4]2[NH2:1])=[CH:11][C:12]=1[F:17]

Participants

5

Reactant 3

HCID 8028TetrahydrofuranHCID 11776TriphenylphosphineHCID 86705585trans-(+)-3-Azido-4-(4-chloro-3-fluorophenoxy)-1-methylpyrrolidine

Product 1

HCID 86705587trans-(+/-)-4-(4-Chloro-3-fluorophenoxy)-1-methylpyrrolidin-3-amineYield 21%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To a solution of 426 (0.480 g, 1.77 mmol), PPh3 (0.930 g, 3.54 mmol) and THF (10 mL) was added H2O (1.0 mL). The resultant mixture was heated at 55° C. for 3 h. The solvent was removed in vacuo. The residue was purified by SiO2 chromatography eluting with DCM/MeOH (5:1 DCM/MeOH then 1:1) to afford 85 mg (21% over 5 steps) of trans-(±)-4-(4-chloro-3-fluorophenoxy)-1-methylpyrrolidin-3-amine (428): LC-MS (ESI) m/z 245 (M+H).

Workup

  1. customThe solvent was removed in vacuo
  2. customThe residue was purified by SiO2 chromatography
  3. washeluting with DCM/MeOH (5:1 DCM/MeOH

Sources & evidence

ORD record
ord-a78a9eb19c284a8fa6d5850d3aab8a1f
Source dataset
uspto-grants-2015_09
Patent number
US09133187B2

Reaction notes

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