3-Chlorobenzoic Acid → 3-(3-Chloro-5-fluorophenyl)-1-ethylpyrrolidin-3-OL 1-oxide

HRID 1931854Notes

Reaction equation

HRID 1931854 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:9]2([OH:16])[CH2:13][CH2:12][N:11]([CH2:14][CH3:15])[CH2:10]2)[CH:5]=[C:6]([F:8])[CH:7]=1.ClC1C=C(C=CC=1)C(O)=[O:22]>ClCCl>[Cl:1][C:2]1[CH:3]=[C:4]([C:9]2([OH:16])[CH2:13][CH2:12][N+:11]([O-:22])([CH2:14][CH3:15])[CH2:10]2)[CH:5]=[C:6]([F:8])[CH:7]=1

Participants

4

Reactant 2

HCID 4473-Chlorobenzoic AcidHCID 251457773-(3-Chloro-5-fluorophenyl)-1-ethylpyrrolidin-3-ol

Product 1

HCID 866434273-(3-Chloro-5-fluorophenyl)-1-ethylpyrrolidin-3-OL 1-oxideYield 64.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

3-(3-chloro-5-fluorophenyl)-1-ethylpyrrolidin-3-ol (0.65 g, 2.67 mmol) was dissolved in dichloromethane (30 ml) and m-chlorobenzoic acid (1.38 g, 8.01 mmol) was added in portions. The mixture was stirred at ambient temperature for 15 h after which about 75% of the solvent was evaporated. The resulting slurry was purified with flash chromatography on basic Al2O3 eluted with methanol. The methanol was evaporated and dichloromethane (50 ml) and aqueous sodium carbonate (10%, 50 mL) was added. The organic phase was dried (MgSO4) and evaporated to give the title compound (0.45 g). The amine was converted to the hydrochloric acid salt and recrystallized from ethanol/diethyl ether: M.p. 158-160° C.

Workup

  1. customwas evaporated
  2. customThe resulting slurry was purified with flash chromatography on basic Al2O3
  3. washeluted with methanol
  4. customThe methanol was evaporated
  5. additiondichloromethane (50 ml) and aqueous sodium carbonate (10%, 50 mL) was added
  6. dry with materialThe organic phase was dried (MgSO4)
  7. customevaporated

Sources & evidence

ORD record
ord-6e38bfe9c24c4026987847e7f4b19380
Source dataset
uspto-grants-2012_05
Patent number
US08188301B2

Reaction notes

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