Tris(1,1-dimethylethyl)phosphine → (1R)-1'-{[1-(4-pyridin-4-ylphenyl)cyclopropyl]carbonyl}-3H-spiro[2-benzofuran-1,3'-pyrrolidin]-3-one

HRID 969095Notes

Reaction equation

HRID 969095 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)=[CH:4][CH:3]=1.C([Sn](CCCC)(CCCC)[C:32]1[CH:37]=[CH:36][N:35]=[CH:34][CH:33]=1)CCC.C(P(C(C)(C)C)C(C)(C)C)(C)(C)C.[F-].[K+]>O1CCCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[N:35]1[CH:36]=[CH:37][C:32]([C:2]2[CH:3]=[CH:4][C:5]([C:8]3([C:11]([N:13]4[CH2:17][CH2:16][C@@:15]5([C:21]6[CH:22]=[CH:23][CH:24]=[CH:25][C:20]=6[C:19](=[O:26])[O:18]5)[CH2:14]4)=[O:12])[CH2:10][CH2:9]3)=[CH:6][CH:7]=2)=[CH:33][CH:34]=1

Participants

7

Reactant 4

HCID 83681Tris(1,1-dimethylethyl)phosphineHCID 522689Potassium FluorideHCID 27373184-(Tri-n-butylstannyl)pyridineHCID 66661876(1R)-1'-{[1-(4-bromophenyl)cyclopropyl]-carbonyl}-3H-spiro[2-benzofuran-1,3'-pyrrolidin]-3-one

Product 1

HCID 66661645(1R)-1'-{[1-(4-pyridin-4-ylphenyl)cyclopropyl]carbonyl}-3H-spiro[2-benzofuran-1,3'-pyrrolidin]-3-oneYield 13%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 8028TetrahydrofuranSolvent

Procedure

A mixture of (1R)-1′-{[1-(4-bromophenyl)cyclopropyl]carbonyl}-3H-spiro[2-benzofuran-1,3′-pyrrolidin]-3-one (25 mg, 0.061 mmol), 4-(tributylstannyl)pyridine (24 mg, 0.067 mmol), tris(dibenzylideneacetone)dipalladium(0) (3 mg, 0.003 mmol), tri-tert-butylphosphine (1.5 mg, 0.007 mmol), and potassium fluoride (12 mg, 0.20 mmol) in tetrahydrofuran (0.3 ml) was microwave irradiated at 90° C. for 15 minutes. Then the desired product was obtained from the mixture by prep-HPLC (3.2 mg, yield: 13%). LCMS: m/z 411.1 (M+H)+; 433.0(M+Na)+.

Workup

  1. customwas microwave irradiated at 90° C. for 15 minutes

Sources & evidence

ORD record
ord-3887a48a02e84bb9b6ccd9cdba8a30b3
Source dataset
uspto-grants-2007_12
Patent number
US07304081B2

Reaction notes

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