Bromocyclopentane → HCID 67071673, compound

HRID 874334Notes

Reaction equation

HRID 874334 reaction equation
[CH3:1][O:2][C:3](=[O:29])/[CH:4]=[CH:5]/[C:6]1[CH:7]=[C:8]2[C:25](=[CH:26][CH:27]=1)[O:24][C:11]1([CH2:16][CH2:15][CH2:14][N:13]([C:17](OC(C)(C)C)=O)[CH2:12]1)[CH2:10][C:9]2=[O:28].Br[CH:31]1[CH2:35]C[CH2:33][CH2:32]1.C([O-])([O-])=O.[K+].[K+]>CC#N>[CH3:1][O:2][C:3](=[O:29])/[CH:4]=[CH:5]/[C:6]1[CH:7]=[C:8]2[C:25](=[CH:26][CH:27]=1)[O:24][C:11]1([CH2:16][CH2:15][CH2:14][N:13]([CH:17]3[CH2:33][CH2:32][CH2:31][CH2:35]3)[CH2:12]1)[CH2:10][C:9]2=[O:28]

Participants

5

Reactant 3

HCID 8728Bromocyclopentane2×HCID 11430Potassium CarbonateHCID 67071461HCID 67071461, compound2×

Product 1

HCID 67071673HCID 67071673, compoundYield 87.2%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
75 °C

Procedure

A mixture of (±)-(E)-3-[4-oxo-spiro(chromane-2,3′-piperidine)-6-yl]-acrylic acid methyl ester hydrochloride (Intermediate 2, 300 mg, 0.888 mmol), bromocyclopentane (397 mg, 2.66 mmol) and K2CO3 (491 mg, 3.55 mmol) in CH3CN (40 ml) was stirred at 75° C. Further bromocyclopentane (397 mg, 2.66 mmol) and catalytical amount of KI were added over three days. The solvent was removed and the residue was partitioned between EtOAc and H2O. The organic layer was dried over Na2SO4 and evaporated to dryness. The crude product was purified by column chromatography (eluent: DCM/MeOH 98:2) to give (±)-(E)-3-[1′-cyclopentyl-4-oxo-spiro(chromane-2,3′-piperidine)-6-yl]-acrylic acid methyl ester (286 mg).

Workup

  1. customThe solvent was removed
  2. customthe residue was partitioned between EtOAc and H2O
  3. dry with materialThe organic layer was dried over Na2SO4
  4. customevaporated to dryness
  5. customThe crude product was purified by column chromatography (eluent: DCM/MeOH 98:2)

Sources & evidence

ORD record
ord-3a7abd55b84341c7a022c63a9fdfea28
Source dataset
uspto-grants-2015_03
Patent number
US08980877B2

Reaction notes

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