Hydrochloric Acid → 1-[4-(4-Chloro-phenoxy)-phenyl]-5-(3-trifluoromethyl-phenyl)-pyrrolidin-2-one

HRID 1972189Notes

Reaction equation

HRID 1972189 reaction equation
N(OC(C)(C)C)=O.N[C:9]1[CH:14]=[CH:13][C:12]([CH:15]2[N:19]([C:20]3[CH:25]=[CH:24][C:23]([O:26][C:27]4[CH:32]=[CH:31][C:30]([Cl:33])=[CH:29][CH:28]=4)=[CH:22][CH:21]=3)[C:18](=[O:34])[CH2:17][CH2:16]2)=[CH:11][C:10]=1[C:35]([F:38])([F:37])[F:36].Cl>CN(C=O)C>[Cl:33][C:30]1[CH:29]=[CH:28][C:27]([O:26][C:23]2[CH:24]=[CH:25][C:20]([N:19]3[CH:15]([C:12]4[CH:13]=[CH:14][CH:9]=[C:10]([C:35]([F:36])([F:37])[F:38])[CH:11]=4)[CH2:16][CH2:17][C:18]3=[O:34])=[CH:21][CH:22]=2)=[CH:32][CH:31]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 10906Tert-Butyl nitriteHCID 594859225-(4-Amino-3-trifluoromethyl-phenyl)-1-[4-(4-chloro-phenoxy)-phenyl]-pyrrolidin-2-one

Product 1

HCID 594860141-[4-(4-Chloro-phenoxy)-phenyl]-5-(3-trifluoromethyl-phenyl)-pyrrolidin-2-oneYield 73.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
65 °C

Procedure

A solution of t-butyl nitrite (4.62 mg, 0.045 mmol) in DMF (0.2 mL) is heated to 65° C. while 5-(4-amino-3-trifluoromethyl-phenyl)-1-[4-(4-chloro-phenoxy)-phenyl]-pyrrolidin-2-one (10 mg, 0.022 mmol) in DMF (0.2 mL) is added in dropwise. The resulted mixture is stirred at 65° C. for an extra 5 min and then cooled down to room temperature. The reaction mixture is treated with 2 N HCl (5 mL) and extracted with EtOAc (3×3 mL). The combined organic layers is concentrated and purified by flash column chromatography (silica gel, EtOAc/hexane 0˜50%) to provide the title compound 1-[4-(4-chloro-phenoxy)-phenyl]-5-(3-trifluoromethyl-phenyl)-pyrrolidin-2-one as colorless oil (˜7 mg, 72%). 1H NMR (CDCl3, 400 MHz) δ 7.53 (d, 1H), 7.47 (s, 1H), 7.46 (d, 1H), 7.41 (t, 1H), 7.31 (d, 2H), 7.25 (d, 2H), 6.88 (d, 2H), 6.86 (d, 2H), 5.28 (t, 1H), 2.60-2.80 (m, 3H), 1.99-2.02 (m, 1H); HPLC-MS calculated for C23H17ClF3NO2 (M+H+) 432.1, found 432.1.

Workup

  1. additionis added in dropwise
  2. temperaturecooled down to room temperature
  3. extractionextracted with EtOAc (3×3 mL)
  4. concentrationThe combined organic layers is concentrated
  5. custompurified by flash column chromatography (silica gel, EtOAc/hexane 0˜50%)

Sources & evidence

ORD record
ord-92ea4be4b1dd497a8f977b2068fb5aed
Source dataset
uspto-grants-2013_04
Patent number
US08431607B2

Reaction notes

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