Trifluoroacetic acid → 5-(2-Amino-3-trifluoromethyl-phenyl)-1-[4-(4-chloro-phenoxy)-phenyl]-pyrrolidin-2-one

HRID 1972188Notes

Reaction equation

HRID 1972188 reaction equation
[Cl:1][C:2]1[CH:21]=[CH:20][C:5]([O:6][C:7]2[CH:12]=[CH:11][C:10]([N:13]3[CH:17]([OH:18])[CH2:16][CH2:15][C:14]3=[O:19])=[CH:9][CH:8]=2)=[CH:4][CH:3]=1.[C:22](O)([C:24]([F:27])([F:26])[F:25])=O>C(Cl)Cl>[NH2:13][C:10]1[CH:9]=[CH:8][C:7]([CH:14]2[N:13]([C:10]3[CH:9]=[CH:8][C:7]([O:6][C:5]4[CH:4]=[CH:3][C:2]([Cl:1])=[CH:21][CH:20]=4)=[CH:12][CH:11]=3)[C:17](=[O:18])[CH2:16][CH2:15]2)=[CH:12][C:22]=1[C:24]([F:27])([F:26])[F:25].[NH2:13][C:10]1[C:22]([C:24]([F:27])([F:26])[F:25])=[CH:12][CH:7]=[CH:8][C:9]=1[CH:17]1[N:13]([C:10]2[CH:11]=[CH:12][C:7]([O:6][C:5]3[CH:4]=[CH:3][C:2]([Cl:1])=[CH:21][CH:20]=3)=[CH:8][CH:9]=2)[C:14](=[O:19])[CH2:15][CH2:16]1

Participants

5

Reactant 2

HCID 6422Trifluoroacetic acidHCID 594856161-[4-(4-Chloro-phenoxy)-phenyl]-5-hydroxy-pyrrolidin-2-one

Product 2

HCID 249487555-(2-Amino-3-trifluoromethyl-phenyl)-1-[4-(4-chloro-phenoxy)-phenyl]-pyrrolidin-2-oneHCID 594859225-(4-Amino-3-trifluoromethyl-phenyl)-1-[4-(4-chloro-phenoxy)-phenyl]-pyrrolidin-2-one

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
40 °C

Procedure

To a mixture of 1-[4-(4-chloro-phenoxy)-phenyl]-5-hydroxy-pyrrolidin-2-one (10 mg, 0.033 mmol) and TFA (0.2 mL) in CH2Cl2 (0.8 mL) is added 3-trifluoroaniline (50 mL). After stirring at 40° C. for 14 h, the mixture is cooled and concentrated. The resulted residue is treated with saturated NaHCO3 aqueous solution (1 mL) and extracted with EtOAc (3×3 mL). The combined organic layers is concentrated and purified by preparative LC/MS to provide the title compound 5-(4-amino-3-trifluoromethyl-phenyl)-1-[4-(4-chloro-phenoxy)-phenyl]-pyrrolidin-2-one as major product (11 mg, 75%, example 2) and 5-(2-amino-3-trifluoromethyl-phenyl)-1-[4-(4-chloro-phenoxy)-phenyl]-pyrrolidin-2-one as minor product (2.52 mg, 17%, example 5). Example 2: 1H NMR (CDCl3, 400 MHz) δ 7.27 (d, 2H), 7.23 (d, 1H), 7.17 (d, 2H), 7.14 (dd, 1H), 6.89 (d, 2H), 6.88 (d, 2H), 6.71 (d, 1H), 6.02 (br, 2H), 5.14 (dd, 1H), 2.64-3.0 (m, 3H), 2.05-2.13 (m, 1H); HPLC-MS calculated for C23H18ClF3N2O2 (M+H+) 447.1, found 447.1. Example 5: 1H NMR (CDCl3, 400 MHz) δ 7.40 (d, 3H), 7.25 (d, 2H), 7.15 (d, 2H), 7.14 (dd, 1H), 6.90 (d, 2H), 6.88 (d, 2H), 6.76 (t, 1H), 5.25 (dd, 1H), 4.24 (br, 2H), 2.56-2.80 (m, 3H), 2.05-2.18 (m, 1H); HPLC-MS calculated for C23H18ClF3N2O2 (M+H+) 447.1, found 447.1.

Workup

  1. temperaturethe mixture is cooled
  2. concentrationconcentrated
  3. additionThe resulted residue is treated with saturated NaHCO3 aqueous solution (1 mL)
  4. extractionextracted with EtOAc (3×3 mL)
  5. concentrationThe combined organic layers is concentrated
  6. custompurified by preparative LC/MS

Sources & evidence

ORD record
ord-cc9ff3ebd8a5436f9925bad03f332416
Source dataset
uspto-grants-2013_04
Patent number
US08431607B2

Reaction notes

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