Tetrahydrofuran → (1R)-1'-({1-[4-(3,5-dimethylisoxazol-4-yl)phenyl]cyclopropyl}carbonyl)-3H-spiro[2-benzofuran-1,3'-pyrrolidin]-3-one

Participants

Role	Name	HCID	Charge
Reactant	Tetrahydrofuran	HCID 8028	—
Reactant	Tris(1,1-dimethylethyl)phosphine	HCID 83681	—
Reactant	Potassium Fluoride	HCID 522689	—
Reactant	3,5-Dimethylisoxazole-4-boronic acid pinacol ester	HCID 2758656	—
Reactant	(1R)-1'-{[1-(4-bromophenyl)cyclopropyl]-carbonyl}-3H-spiro[2-benzofuran-1,3'-pyrrolidin]-3-one	HCID 66661876	—
Catalyst	Bis(dibenzylideneacetone)palladium	HCID 9811564	—
Product	(1R)-1'-({1-[4-(3,5-dimethylisoxazol-4-yl)phenyl]cyclopropyl}carbonyl)-3H-spiro[2-benzofuran-1,3'-pyrrolidin]-3-one	HCID 66661768	—

Reaction Conditions

Temperature	150 °C

Reaction Steps

To a solution of (1R)-1′-{[1-(4-bromophenyl)cyclopropyl]carbonyl}-3H-spiro[2-benzofuran-1,3′-pyrrolidin]-3-one (20 mg, 0.00005 mol) in tetrahydrofuran (1.0 mL, 0.012 mol) were added 3,5-dimethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)isoxazole (11.9 mg, 0.0000534 mol), tris(dibenzylideneacetone)dipalladium(0) (0.2 mg, 0.0000002 mol), tri-tert-butylphosphine (0.12 mg, 5.8E-7 mol) and potassium fluoride (9.3 mg, 0.00016 mol), and the resulting mixture was heated at 150 Celsius under microwave for 50 minutes. The mixture then was cooled down to r.t. and filtered. The filtrate was diluted with methanol, and the desired compound was obtained by revised phase prep-HPLC. MS (ESI): 429.2 (M+H+).

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US08058288B2
Source dataset	uspto-grants-2011_11
ORD ID	ord-ab2fffbd89104f4abd9c0230643f4af9
Source note	uspto-grants-2011_11