Ammonium Chloride → Rac-3-hydroxy-3-(4-trifluoromethyl-phenyl)-pyrrolidine-1-carboxylic acid ethyl ester

HRID 552677Notes

Reaction equation

HRID 552677 reaction equation
[Mg].Br[C:3]1[CH:8]=[CH:7][C:6]([C:9]([F:12])([F:11])[F:10])=[CH:5][CH:4]=1.[CH2:13]([O:15][C:16]([N:18]1[CH2:22][CH2:21][C:20](=[O:23])[CH2:19]1)=[O:17])[CH3:14].[NH4+].[Cl-]>CCOCC>[CH2:13]([O:15][C:16]([N:18]1[CH2:22][CH2:21][C:20]([OH:23])([C:3]2[CH:8]=[CH:7][C:6]([C:9]([F:12])([F:11])[F:10])=[CH:5][CH:4]=2)[CH2:19]1)=[O:17])[CH3:14]

Participants

6

Reactant 4

HCID 25517Ammonium ChlorideHCID 67872Benzene, 1-bromo-4-(trifluoromethyl)-2×HCID 277754Ethyl 3-oxopyrrolidine-1-carboxylateHCID 5462224Magnesium

Product 1

HCID 59030467Rac-3-hydroxy-3-(4-trifluoromethyl-phenyl)-pyrrolidine-1-carboxylic acid ethyl esterYield 61%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent3×

Conditions

Temperature
0 °C

Procedure

364 mg magnesium was suspended in 2 ml ether, under nitrogen. 150 ul 4-bromobenzo-trifluoride was added and then a solution of 12.6 mmol 4-bromobenzotrifluoride in 1.5 ml ether was added dropwise over a period of 10 minutes at room temperature. The mixture came mildly exothermic and turned red-brown while the grignard reagent formed during 1.5 h of stirring. The mixture was cooled down to 0° C. A solution of 12.5 mmol 1-N-ethoxycarbonyl-3-pyrrolidone in 14 ml ether was added dropwise. The reaction mixture was allowed to come to room temperature and stirred for 2 h30. 20% NH4Cl was added dropwise, at 0° C., to quench the reaction. The mixture was allowed to warm to room temperature. The aqueous layer was extracted 3 times with ether. The combined organic phases were washed with water and brine, dried over Na2SO4 and evaporated. The residue was purified on silica gel (eluent: heptane-ethyl acetate 1/1) to yield the title compound (61%) as a yellow solid. MS (m/e): 362.2 ([M+59], 100%).

Workup

  1. customformed during 1.5 h
  2. customto come to room temperature
  3. stirringstirred for 2 h30
  4. customto quench
  5. customthe reaction
  6. temperatureto warm to room temperature
  7. extractionThe aqueous layer was extracted 3 times with ether
  8. washThe combined organic phases were washed with water and brine
  9. dry with materialdried over Na2SO4
  10. customevaporated
  11. customThe residue was purified on silica gel (eluent: heptane-ethyl acetate 1/1)

Sources & evidence

ORD record
ord-212c8e50853249e2952be591413f6ade
Source dataset
uspto-grants-2011_05
Patent number
US07951836B2

Reaction notes

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