Dimethylformamide → HCID 118071099, compound

HRID 920716Notes

Reaction equation

HRID 920716 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C:8]2[C:23](I)=[C:11]3[CH2:12][N:13]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:14][CH2:15][N:10]3[N:9]=2)[CH:5]=[CH:6][CH:7]=1.[CH3:25][N:26](C=O)C>[C-]#N.[Zn+2].[C-]#N.[Zn].C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.[Fe+2]>[C:25]([C:23]1[C:8]([C:4]2[CH:5]=[CH:6][CH:7]=[C:2]([F:1])[CH:3]=2)=[N:9][N:10]2[CH2:15][CH2:14][N:13]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:12][C:11]=12)#[N:26]

Participants

7

Reactant 2

HCID 6228DimethylformamideHCID 118071097HCID 118071097, compound

Product 1

HCID 118071099HCID 118071099, compoundYield 78%

Reagents, catalysts & solvents 4

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 23994ZincCatalystHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst

Conditions

Temperature
90 °C

Procedure

To a solution of Intermediate 4G (5.0 g, 11.28 mmol) in DMF (50 mL) was added zinc cyanide (1.722 g, 14.66 mmol) and zinc (0.221 g, 3.38 mmol) to give a brown suspension. The reaction mixture was degassed under nitrogen for 15 min and added Pd2(dba)3 (0.516 g, 0.564 mmol) and dppf (0.625 g, 1.128 mmol). The reaction mixture was stirred at 90° C. for 18 h. The reaction mixture was quenched with water and the aqueous layer was extracted with ethyl acetate (3×50 mL) The combined organic layer was and washed with aqueous ammonia (2×50 mL), water, dried over Na2SO4, filtered and concentrated to afford crude product as brown semi-solid. The crude was purified by silica gel chromatography (40 g REDISEP® column, eluting with 50% EtOAc in hexane). Collected fractions concentrated together to afford Intermediate 4H (3 g, 78%) as white solid. MS(ES): m/z=343 [M+H]+; 1H NMR (400 MHz, CDCl3) δ ppm 7.73-7.78 (m, 1H), 7.62-7.68 (m, 1H), 7.43 (td, J=8.03, 5.52 Hz, 1H), 7.08-7.15 (m, 1H), 4.82 (s, 2H), 4.24 (t, J=5.52 Hz, 2H), 3.96 (t, J=5.27 Hz, 2H), 1.52 (s, 9H).

Workup

  1. customto give a brown suspension
  2. customThe reaction mixture was degassed under nitrogen for 15 min
  3. customThe reaction mixture was quenched with water
  4. extractionthe aqueous layer was extracted with ethyl acetate (3×50 mL) The combined organic layer
  5. washwashed with aqueous ammonia (2×50 mL), water
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customto afford crude product as brown semi-solid
  10. customThe crude was purified by silica gel chromatography (40 g REDISEP® column, eluting with 50% EtOAc in hexane)
  11. customCollected
  12. concentrationfractions concentrated together

Sources & evidence

ORD record
ord-d4fa9aa323b44b48975eb0554ec23c7b
Source dataset
uspto-grants-2016_03
Patent number
US09273058B2

Reaction notes

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