Potassium Carbonate → (1R)-1'-({1-[2-Fluoro-4-(2-oxopyrrolidin-1-yl)phenyl]cyclopropyl}carbonyl)-3H-spiro[2-benzofuran-1,3'-pyrrolidin]-3-one

HRID 504374Notes

Reaction equation

HRID 504374 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]2([C:11]([N:13]3[CH2:17][CH2:16][C@@:15]4([C:21]5[CH:22]=[CH:23][CH:24]=[CH:25][C:20]=5[C:19](=[O:26])[O:18]4)[CH2:14]3)=[O:12])[CH2:10][CH2:9]2)=[C:4]([F:27])[CH:3]=1.[NH:28]1[CH2:32][CH2:31][CH2:30][C:29]1=[O:33].[C@@H]1(N)CCCC[C@H]1N.C(=O)([O-])[O-].[K+].[K+]>C1(C)C=CC=CC=1.CN(C)C=O.[Cu]I>[F:27][C:4]1[CH:3]=[C:2]([N:28]2[CH2:32][CH2:31][CH2:30][C:29]2=[O:33])[CH:7]=[CH:6][C:5]=1[C:8]1([C:11]([N:13]2[CH2:17][CH2:16][C@@:15]3([C:21]4[CH:22]=[CH:23][CH:24]=[CH:25][C:20]=4[C:19](=[O:26])[O:18]3)[CH2:14]2)=[O:12])[CH2:10][CH2:9]1

Participants

8

Reactant 4

HCID 11430Potassium CarbonateHCID 120252-PyrrolidoneHCID 438061,2-Diaminocyclohexane, trans-HCID 66662680(1R)-1'-{[1-(4-bromo-2-fluorophenyl)cyclopropyl]carbonyl}-3H-spiro[2-benzofuran-1,3'-pyrrolidin]-3-one

Product 1

HCID 66662364(1R)-1'-({1-[2-Fluoro-4-(2-oxopyrrolidin-1-yl)phenyl]cyclopropyl}carbonyl)-3H-spiro[2-benzofuran-1,3'-pyrrolidin]-3-one

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 1140TolueneSolventHCID 6228DimethylformamideSolvent

Procedure

A mixture of (1R)-1′-{[1-(4-bromo-2-fluorophenyl)cyclopropyl]carbonyl}-3H-spiro[2-benzofuran-1,3′-pyrrolidin]-3-one (10 mg, 0.00002 mol, prepared by methods analogous to those used for the synthesis of example 238), 2-pyrrolidinone (2.4 mg, 0.000028 mol), copper(I) iodide (0.2 mg, 0.000001 mol), trans-1,2-cyclohexanediamine (0.28 μL, 0.0000023 mol), and potassium carbonate (6.4 mg, 0.000046 mol) in toluene (0.5 mL) and N,N-dimethylformamide (0.5 mL) was microwave irradiated at 110° C. for 30 minutes. The crude product was purified with prep-HPLC. LCMS: m/z 435.2 (M+H+); 457.1 (M+Na+).

Workup

  1. customprepared by methods analogous to
  2. customwas microwave irradiated at 110° C. for 30 minutes
  3. customThe crude product was purified with prep-HPLC

Sources & evidence

ORD record
ord-fe3e5e3f2dcd45e2baecad0673a5174c
Source dataset
uspto-grants-2010_08
Patent number
US07776874B2

Reaction notes

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