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

HRID 504336Notes

Reaction equation

HRID 504336 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.[NH:27]1[CH2:31][CH2:30][CH2:29][CH2:28]1.N12CCCN=C1CCCCC2.[O:43]1CCC[CH2:44]1>[C-]#[O+].[C-]#[O+].[C-]#[O+].[C-]#[O+].[C-]#[O+].[C-]#[O+].[Mo].CC1C(P(C2C([CH2-])=CC=CC=2)C2C(C)=CC=CC=2)=CC=CC=1.CC1C(P(C2C([CH2-])=CC=CC=2)C2C(C)=CC=CC=2)=CC=CC=1.CC(O)=O.CC(O)=O.[Pd].[Pd]>[N:27]1([C:44]([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)=[O:43])[CH2:31][CH2:30][CH2:29][CH2:28]1

Participants

7

Reactant 4

HCID 8028TetrahydrofuranHCID 31268PyrrolidineHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 66661876(1R)-1'-{[1-(4-bromophenyl)cyclopropyl]-carbonyl}-3H-spiro[2-benzofuran-1,3'-pyrrolidin]-3-one

Product 1

HCID 66662255(1R)-1'-({1-[4-(Pyrrolidin-1-ylcarbonyl)phenyl]cyclopropyl}carbonyl)-3H-spiro[2-benzofuran-1,3'-pyrrolidin]-3-oneYield 79%

Reagents, catalysts & solvents 2

HCID 98885Molybdenum carbonyl (Mo(CO)6)CatalystHCID 11104995trans-Bis(acetato)bis[2-[bis(2-methylphenyl)phosphino]benzyl]dipalladium(II)Catalyst

Procedure

A mixture of (1R)-1′-{[1-(4-bromophenyl)cyclopropyl]carbonyl}-3H-spiro[2-benzofuran-1,3′-pyrrolidin]-3-one (68.0 mg, 0.000165 mol, example 238), pyrrolidine (42 μL, 0.00049 mol), molybdenum hexacarbonyl (44 mg, 0.00016 mol), trans-di(μ-acetato)bis[o-(di-o-tolylphosphino)benzyl]dipalladium (II) (16 mg, 0.000016 mol) and 1,8-diazabicyclo[5.4.0] undec-7-ene (76 μL, 0.00049 mol) (DBU) in anhydrous tetrahydrofuran (2.0 mL, 0.025 mol) in a microwave vial was irradiated with microwaves to 150° C. for 30 minutes. The reaction mixture was filtered. The filtrate was purified by prep-HPLC to afford the product as a solid (55.9 mg, 79% in yield). LC/MS (M+H+)=431.1.

Workup

  1. customwas irradiated with microwaves to 150° C. for 30 minutes
  2. filtrationThe reaction mixture was filtered
  3. customThe filtrate was purified by prep-HPLC

Sources & evidence

ORD record
ord-39c2631f60514bbfbc96d19f8f906d55
Source dataset
uspto-grants-2010_08
Patent number
US07776874B2

Reaction notes

Loading…