Dimethylformamide → HCID 86722069, compound

HRID 1507767Notes

Reaction equation

HRID 1507767 reaction equation
[CH2:1]([O:8][C:9](=[O:27])[NH:10][CH:11]([CH3:26])[CH2:12][CH2:13][CH2:14][C:15]1[CH:20]=[C:19]([C:21]([F:24])([F:23])[F:22])[CH:18]=[C:17](Cl)[N:16]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CN(C=O)C.[CH3:33][CH2:34]N(CC)CC.C([O-])([O-])=O.[K+].[K+]>CCOC(C)=O.CO.[Cu]I.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH2:1]([O:8][C:9](=[O:27])[NH:10][CH:11]([CH3:26])[CH2:12][CH2:13][CH2:14][C:15]1[CH:20]=[C:19]([C:21]([F:24])([F:23])[F:22])[CH:18]=[C:17]([C:33]#[CH:34])[N:16]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

9

Reactant 4

HCID 6228DimethylformamideHCID 8471TriethylamineHCID 11430Potassium CarbonateHCID 86722070HCID 86722070, compound

Product 1

HCID 86722069HCID 86722069, compoundYield 100%

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 887MethanolSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
70 °C

Procedure

A mixture of 4 (470 mg, 1.17 mmol, 1 eq), CuI (23 mg, 0.117 mmol, 0.1 eq.), Pd(PPh3)4 (68 mg, 0.058 mmol, 0.05 eq.) and DMF (8 mL) was degassed. Trimethsilyacetylene (173 mg, 1.760 mmol, 1.5 eq.) was added under Argon, followed by Et3N (356 mg, 4.81 mL, 3.52 mmol, 3 eq.). The mixture was heated at 70° C. for 24 h. After being cooled to room temperature, the reaction mixture was diluted with EtOAc (50 mL) and washed with brine (20 mL×2). The EtOAc solution was dried over MgSO4, filtered and concentrated. The crude product was purified by flash chromatography (0-30%, EtOAc in heptane) to afford the desired trimethsilyacetylene derivative (500 mg, 92%). The product was dissolved in MeOH (20 mL), and K2CO3 (138 mg, 1 mmol) was added. The reaction mixture was stirred at room temperature for 30 min before concentration. The residue was partitioned between EtOAc (20 mL) and H2O (20 mL). The EtOAc layer was washed with brine (10 mL), dried over MgSO4, filtered and concentrated. The crude product was purified by flash chromatography (0-50%, EtOAc in heptane) to afford 5 as colorless oil (423 mg, 100%).

Workup

  1. customwas degassed
  2. additionTrimethsilyacetylene (173 mg, 1.760 mmol, 1.5 eq.) was added under Argon
  3. temperatureAfter being cooled to room temperature
  4. washwashed with brine (20 mL×2)
  5. dry with materialThe EtOAc solution was dried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe crude product was purified by flash chromatography (0-30%, EtOAc in heptane)
  9. customto afford the desired trimethsilyacetylene derivative (500 mg, 92%)
  10. customThe residue was partitioned between EtOAc (20 mL) and H2O (20 mL)
  11. washThe EtOAc layer was washed with brine (10 mL)
  12. dry with materialdried over MgSO4
  13. filtrationfiltered
  14. concentrationconcentrated
  15. customThe crude product was purified by flash chromatography (0-50%, EtOAc in heptane)

Sources & evidence

ORD record
ord-058f5fbba9c441509b18585d28de2171
Source dataset
uspto-grants-2015_12
Patent number
US09221827B2

Reaction notes

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