Trifluoroacetic acid → 4-[3-(1-Aminoethyl)-5-chloro-2-methoxy-6-methylphenyl]pyrrolidin-2-one

HRID 511018Notes

Reaction equation

HRID 511018 reaction equation
[Cl:1][C:2]1[C:3]([CH3:26])=[C:4]([CH:20]2[CH2:24][C:23](=[O:25])[NH:22][CH2:21]2)[C:5]([O:18][CH3:19])=[C:6]([CH:8]([NH:10]C(=O)OC(C)(C)C)[CH3:9])[CH:7]=1.FC(F)(F)C(O)=O>C(Cl)Cl>[NH2:10][CH:8]([C:6]1[C:5]([O:18][CH3:19])=[C:4]([CH:20]2[CH2:21][NH:22][C:23](=[O:25])[CH2:24]2)[C:3]([CH3:26])=[C:2]([Cl:1])[CH:7]=1)[CH3:9]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 86666939Tert-butyl {1-[5-chloro-2-methoxy-4-methyl-3-(5-oxopyrrolidin-3-yl)phenyl]ethyl}carbamate

Product 1

HCID 866669384-[3-(1-Aminoethyl)-5-chloro-2-methoxy-6-methylphenyl]pyrrolidin-2-one

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Solutions of the individual diastereoisomers of tert-butyl {1-[5-chloro-2-methoxy-4-methyl-3-(5-oxopyrrolidin-3-yl)phenyl]ethyl}carbamate (75 mg, 0.20 mmol [peak 1 from step 3]; 75 mg, 0.20 mmol [peak 2 from step 3]) in separate reaction flasks in methylene chloride (1 mL) were each treated individually with trifluoroacetic acid (1 mL) dropwise and stirred for 30 minutes. The reaction mixtures were individually concentrated to residues, diluted with saturated sodium bicarbonate, and extracted several times with dichloromethane to give diastereoisomer from peak 1 (60 mg, quantitative) and diastereoisomer from peak 2 (55 mg, quantitative) as colorless residues that were used without further purification. Peak 1: LCMS for C14H17ClNO2 (M−NH2)+: m/z=266.1. Found: 266.1. Peak 2: LCMS for C14H20ClN2O2 (M+H)+: m/z=283.1. Found: 283.1.

Workup

  1. customThe reaction mixtures
  2. concentrationwere individually concentrated to residues
  3. additiondiluted with saturated sodium bicarbonate
  4. extractionextracted several times with dichloromethane
  5. customto give diastereoisomer from peak 1 (60 mg, quantitative) and diastereoisomer from peak 2 (55 mg, quantitative) as colorless residues that
  6. customwere used without further purification

Sources & evidence

ORD record
ord-6bd4219a31184523867a167a5bb3b5ae
Source dataset
uspto-grants-2015_08
Patent number
US09096600B2

Reaction notes

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