Dimethylformamide → HCID 69152125, compound

HRID 2213337Notes

Reaction equation

HRID 2213337 reaction equation
[CH2:1]([O:8][C:9](=[O:31])[NH:10][CH:11]1[C:17](=[O:18])[N:16]([CH3:19])[C:15]2[CH:20]=[CH:21][CH:22]=[CH:23][C:14]=2[C:13]([C:24]2[CH:29]=[CH:28][C:27](Br)=[CH:26][CH:25]=2)=[N:12]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C1(P(C2C=CC=CC=2)CCCP(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C[Si](C)(C)N[Si](C)(C)C.C(N(CC)C(C)C)(C)C.C[N:80]([CH:82]=[O:83])C>C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH2:1]([O:8][C:9](=[O:31])[NH:10][CH:11]1[C:17](=[O:18])[N:16]([CH3:19])[C:15]2[CH:20]=[CH:21][CH:22]=[CH:23][C:14]=2[C:13]([C:24]2[CH:29]=[CH:28][C:27]([C:82](=[O:83])[NH2:80])=[CH:26][CH:25]=2)=[N:12]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

7

Reactant 5

HCID 6228DimethylformamideHCID 13838HexamethyldisilazaneHCID 812191,3-Bis(diphenylphosphino)propaneHCID 81531DiisopropylethylamineHCID 69150664HCID 69150664, compound

Product 1

HCID 69152125HCID 69152125, compound

Reagents, catalysts & solvents 1

HCID 167845palladium(II) acetateCatalyst

Procedure

A solution of the product from Step 2B (3.5 g, 0.0073 moles), 1,3-bis(diphenylphosphino)propane (305 mg, 0.0073 moles), hexamethyldisilazane (10.8 ml, 0.0146 moles), and N,N-diisopropylethylamine (2.5 ml, 0.0146) in DMF were degassed with nitrogen bubbling for ten minutes. Palladium (II) acetate (162 mg, 0.00073 moles) was added and the mixture degassed for a further five minutes. Carbon monoxide gas was bubbled through the reaction mixture for 5 minutes at room temperature and then for 6 hours at 110° C. After this time, the reaction mixture was cooled and partitioned between dichloromethane (50 ml) and water (50 ml). The aqueous layer was extracted with further dichloromethane (3×50 ml) and the combined organic layers washed with water (100 ml) and brine (100 ml), dried (MgSO4) and vaporated in vacuo. The residue was taken up in a mixture of THF (150 ml) and 2M HCl (30 ml) and stirred at ambient temperature for one hour. The THF was then evaporated in vacuo and the residue partitioned between dichloromethane (50 ml) and 2M NaOH (50 ml). The aqueous layer was extracted with dichloromethane (2×50 ml) and the combined organic layers washed (H2O, brine), dried (MgSO4) and evaporated in vacuo. Purification by chromatography (SiO2, 1% MeOH/CHCl3) gave the title compound. 1H NMR (DMSO-d6) 3.31 (3H, s), 5.07 (2H, s), 5.12 (1H, d), 7.30–7.80 (12H, m), 7.93 (2H, d, J=8.4 Hz), 8.08 (1H, br s), 8.50 (1H, d). MS (ES+) MH+=443

Workup

  1. customthe mixture degassed for a further five minutes
  2. customCarbon monoxide gas was bubbled through the reaction mixture for 5 minutes at room temperature
  3. temperatureAfter this time, the reaction mixture was cooled
  4. custompartitioned between dichloromethane (50 ml) and water (50 ml)
  5. extractionThe aqueous layer was extracted with further dichloromethane (3×50 ml)
  6. washthe combined organic layers washed with water (100 ml) and brine (100 ml)
  7. dry with materialdried (MgSO4)
  8. additionThe residue was taken up in a mixture of THF (150 ml) and 2M HCl (30 ml)
  9. customThe THF was then evaporated in vacuo
  10. customthe residue partitioned between dichloromethane (50 ml) and 2M NaOH (50 ml)
  11. extractionThe aqueous layer was extracted with dichloromethane (2×50 ml)
  12. washthe combined organic layers washed (H2O, brine)
  13. dry with materialdried (MgSO4)
  14. customevaporated in vacuo
  15. customPurification by chromatography (SiO2, 1% MeOH/CHCl3)

Sources & evidence

ORD record
ord-d0a90df5dfb74dfeb134a205952bbf00
Source dataset
uspto-grants-2006_09
Patent number
US07105509B2

Reaction notes

Loading…