Boc-L-Valine → 6-bromo-2H-spiro[benzofuran-3,1'-cyclopentan]-2-one

HRID 2209301Notes

Reaction equation

HRID 2209301 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2([C:13]([OH:15])=[O:14])[CH2:12][CH2:11][CH2:10][CH2:9]2)=[CH:4][CH:3]=1.C(O)(=O)C.C(O)(=O)C.IC1C=CC=CC=1.C(N[C@H](C(O)=O)C(C)C)(OC(C)(C)C)=O.C([O-])(=O)C.[K+]>CC(O)=O.CC(O)=O.[Pd].C(O)(C)(C)C>[Br:1][C:2]1[CH:3]=[CH:4][C:5]2[C:8]3([C:13](=[O:15])[O:14][C:6]=2[CH:7]=1)[CH2:12][CH2:11][CH2:10][CH2:9]3

Participants

7

Reactant 4

HCID 83693Boc-L-ValineHCID 517044Potassium AcetateHCID 8249921-(4-Bromophenyl)cyclopentanecarboxylic acidHCID 12217721Iodo benzene diacetate

Product 1

HCID 1178435586-bromo-2H-spiro[benzofuran-3,1'-cyclopentan]-2-oneYield 37.8%

Reagents, catalysts & solvents 2

HCID 4144353Palladium (II) acetateCatalystHCID 6386tert-ButanolSolvent

Conditions

Temperature
90 °C

Procedure

A vial was charged with 1-(4-bromophenyl)cyclopentanecarboxylic acid (200 mg, 0.743 mmol), iodobenzene diacetate (359 mg, 1.11 mmol), Boc-L-valine (48.4 mg, 0.223 mmol), potassium acetate (146 mg, 1.49 mmol) and palladium (II) acetate trimer (8.34 mg, 5 mol %). Tert-butanol (7.4 mL) was added and the mixture was heated at 90° C. for 11 hours, then at room temperature for 8 hours. The reaction mixture was concentrated, diluted with DCM and filtered. The residue was purified by flash column chromatography on silica gel to afford 6-bromo-2H-spiro[benzofuran-3,1′-cyclopentan]-2-one 7.51 (75 mg). LCMS-ESI+ (m/z): [M+H]+ calcd for C12H1279BrO2: 267.0; found: 267.0.

Workup

  1. concentrationThe reaction mixture was concentrated
  2. additiondiluted with DCM
  3. filtrationfiltered
  4. customThe residue was purified by flash column chromatography on silica gel

Sources & evidence

ORD record
ord-799db47e2f9a4945a2af22724f50b9ef
Source dataset
uspto-grants-2016_06
Patent number
US09376441B2

Reaction notes

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