Dimethylformamide → HCID 57428852, compound

HRID 2267406Notes

Reaction equation

HRID 2267406 reaction equation
FC1C=CC(S[C:9]([S:11][C:12]2[CH:17]=[CH:16][C:15]([F:18])=[CH:14][CH:13]=2)=[S:10])=CC=1.[H-].[Na+].[F:21][C:22]1[CH:27]=[CH:26][C:25]([C:28](=[O:32])[CH2:29][C:30]#[N:31])=[CH:24][CH:23]=1.CN(C=O)C>C1C=CC=CC=1>[C:30]([CH:29]([C:28]([C:25]1[CH:24]=[CH:23][C:22]([F:21])=[CH:27][CH:26]=1)=[O:32])[C:9]([S:11][C:12]1[CH:13]=[CH:14][C:15]([F:18])=[CH:16][CH:17]=1)=[S:10])#[N:31]

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 24758Sodium hydrideHCID 2783172p-FluorobenzoylacetonitrileHCID 86637951HCID 86637951, compound

Product 1

HCID 57428852HCID 57428852, compoundYield 31%

Reagents, catalysts & solvents 1

HCID 241BenzeneSolvent2×

Procedure

Trithiocarbonate (0.644 g, 2.15 mmol) from step (i) was added to a stirred suspension of sodium hydride (0.165 g, 0.412 mmol) in benzene (2.0 mL). Then, 3-(4-fluorophenyl)-3-oxopropanenitrile (0.320 g, 1.96 mmol) was added as a solution in benzene (2.0 mL). The reaction mixture was stirred for 5 min then DMF (2.0 mL) was added slowly. After addition was complete the reaction mixture was heated to reflux for 30 min and then allowed to cool to ambient temperature before being partitioned between H2O and Et2O. The aqueous layer was separated and washed with two additional portions of Et2O, then acidified with aqueous 2 N HCl. The acidic aqueous layer was then extracted with two portions of EtOAc, which were combined, washed with brine, dried over Na2SO4, and concentrated. The residue was purified by flash chromatography, eluting with a gradient of 25-100% EtOAc/hexanes to afford the product as a yellow solid (0.20 g, 0.60 mmol, 31% yield). MS (M−H)− 332.

Workup

  1. additionAfter addition
  2. temperaturewas heated
  3. temperatureto reflux for 30 min
  4. custombefore being partitioned between H2O and Et2O
  5. customThe aqueous layer was separated
  6. washwashed with two additional portions of Et2O
  7. extractionThe acidic aqueous layer was then extracted with two portions of EtOAc, which
  8. washwashed with brine
  9. dry with materialdried over Na2SO4
  10. concentrationconcentrated
  11. customThe residue was purified by flash chromatography
  12. washeluting with a gradient of 25-100% EtOAc/hexanes

Sources & evidence

ORD record
ord-28b00532e45244ad9d471bf1b56f4167
Source dataset
uspto-grants-2010_12
Patent number
US07858785B2

Reaction notes

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