Dimethylformamide → HCID 71115094, compound

HRID 1184728Notes

Reaction equation

HRID 1184728 reaction equation
[CH:1]([O:4][C:5]([N:7]1[CH2:12][CH2:11][CH:10]([CH:13]2[CH2:17][C:16]3[CH:18]=[C:19]([C:22]4[C:27]([CH3:28])=[CH:26][C:25](Br)=[CH:24][N:23]=4)[CH:20]=[CH:21][C:15]=3[O:14]2)[CH2:9][CH2:8]1)=[O:6])([CH3:3])[CH3:2].[CH3:30][N:31](C)C=O>[C-]#N.[Zn+2].[C-]#N.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2]>[CH:1]([O:4][C:5]([N:7]1[CH2:12][CH2:11][CH:10]([CH:13]2[CH2:17][C:16]3[CH:18]=[C:19]([C:22]4[C:27]([CH3:28])=[CH:26][C:25]([C:30]#[N:31])=[CH:24][N:23]=4)[CH:20]=[CH:21][C:15]=3[O:14]2)[CH2:9][CH2:8]1)=[O:6])([CH3:3])[CH3:2]

Participants

5

Reactant 2

HCID 6228DimethylformamideHCID 67973763HCID 67973763, compound

Product 1

HCID 71115094HCID 71115094, compound

Reagents, catalysts & solvents 2

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)Catalyst

Conditions

Temperature
120 °C

Procedure

A mixture of 4-[5-(5-bromo-3-methyl-pyridin-2-yl)-2,3-dihydro-benzofuran-2-yl]-piperidine-1-carboxylic acid isopropyl ester (26 mg), zinc cyanide (7.3 mg), and 1,1′-bis(diphenylphosphino)-ferrocene (3.2 mg) in N,N-dimethylformamide (0.5 mL) is sparged with argon for 5 min. Tris(dibenzylideneacetone)dipalladium (2.6 mg) is added and the resulting mixture is stirred at 120° C. for 3 h. After cooling to room temperature, dichloromethane is added and the mixture is extracted with aqueous K2CO3 solution (10%). The organic phase is washed with brine, dried (MgSO4), and the solvent is evaporated. The residue is chromatographed on silica gel (dichloromethane/methanol 95:5) to give the title compound. Yield: 12 mg (52% of theory); LC (method 2): tR=1.49 min; Mass spectrum (ESI+): m/z=406 [M+H]+.

Workup

  1. customis sparged with argon for 5 min
  2. additionTris(dibenzylideneacetone)dipalladium (2.6 mg) is added
  3. temperatureAfter cooling to room temperature
  4. additiondichloromethane is added
  5. extractionthe mixture is extracted with aqueous K2CO3 solution (10%)
  6. washThe organic phase is washed with brine
  7. dry with materialdried (MgSO4)
  8. customthe solvent is evaporated
  9. customThe residue is chromatographed on silica gel (dichloromethane/methanol 95:5)

Sources & evidence

ORD record
ord-f09ff0749e324fb4b742ed03563e51a5
Source dataset
uspto-grants-2014_03
Patent number
US08669271B2

Reaction notes

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