Dimethylformamide → (1R)-1'-{[1-(4-bromophenyl)cyclopropyl]-carbonyl}-3H-spiro[2-benzofuran-1,3'-pyrrolidin]-3-one

HRID 2275591Notes

Reaction equation

HRID 2275591 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2([C:11]([OH:13])=O)[CH2:10][CH2:9]2)=[CH:4][CH:3]=1.CN(C)C=O.CC1(C)C2CCC1(CS(O)(=O)=O)C(=O)C2.[NH:34]1[CH2:38][CH2:37][C@@:36]2([C:42]3[CH:43]=[CH:44][CH:45]=[CH:46][C:41]=3[C:40](=[O:47])[O:39]2)[CH2:35]1.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.C(N(CC)C(C)C)(C)C>>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2([C:11]([N:34]3[CH2:38][CH2:37][C@@:36]4([C:42]5[CH:43]=[CH:44][CH:45]=[CH:46][C:41]=5[C:40](=[O:47])[O:39]4)[CH2:35]3)=[O:13])[CH2:9][CH2:10]2)=[CH:6][CH:7]=1

Participants

6

Reactant 5

HCID 6228DimethylformamideHCID 81531DiisopropylethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 162279661-(4-Bromophenyl)cyclopropane-1-carboxylic acidHCID 86602281HCID 86602281, compound

Product 1

HCID 66661876(1R)-1'-{[1-(4-bromophenyl)cyclopropyl]-carbonyl}-3H-spiro[2-benzofuran-1,3'-pyrrolidin]-3-oneYield 90%

Procedure

To a stirred solution of 1-(4-bromophenyl)cyclopropanecarboxylic acid (1.616 g, 0.006704 mol) in anhydrous N,N-dimethylformamide (12.0 mL, 0.155 mol) at room temperature was added (7,7-dimethyl-2-oxobicyclo[2.2.1]hept-1-yl)methanesulfonic acid—(1R)-3H-spiro[2-benzofuran-1,3′-pyrrolidin]-3-one (1:1) (2.569 g, 0.006095 mol, example 96, steps 1-2), benzotriazol-1-yloxytris(dimethylamino)phosphonium hexafluorophosphate (3.057 g, 0.006704 mol), followed by N,N-diisopropylethylamine (4.27 mL, 0.0244 mol). The resulting clear solution was stirred at temperature for 17 hours. LCMS showed that the reaction was complete. The reaction was quenched with saturated aqueous NaHCO3 (50 mL), and the reaction mixture was extracted with EtOAc (2×). The combined organic layer was washed with brine, dried over magnesium sulfate, filtered and concentrated in vacuo. The residue was purified by Combiflash with 30-70% EtOAc/hexanes to give the product as a colorless solid (2.258 g, 90% in yield). LC/MS (M+H+)=412.1.

Workup

  1. customThe reaction was quenched with saturated aqueous NaHCO3 (50 mL)
  2. extractionthe reaction mixture was extracted with EtOAc (2×)
  3. washThe combined organic layer was washed with brine
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by Combiflash with 30-70% EtOAc/hexanes

Sources & evidence

ORD record
ord-95f54bc0482f4473a23eb5a44346371d
Source dataset
uspto-grants-2015_09
Patent number
US09126927B2

Reaction notes

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