Sodium Bicarbonate → HCID 25003294, compound

HRID 2176859Notes

Reaction equation

HRID 2176859 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:14]=[CH:15][C:16]=1B1OC(C)(C)C(C)(C)O1)[O:5][C:6]1[CH:11]=[C:10]([CH3:12])[N:9]=[C:8]([CH3:13])[CH:7]=1.C([O-])(O)=O.[Na+].Br[C:32]1[CH:37]=[CH:36][N:35]([CH2:38][CH:39]2[CH2:41][CH2:40]2)[C:34](=[O:42])[C:33]=1[C:43]#[N:44]>O1CCOCC1.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>[CH:39]1([CH2:38][N:35]2[CH:36]=[CH:37][C:32]([C:16]3[CH:15]=[CH:14][C:4]([O:5][C:6]4[CH:7]=[C:8]([CH3:13])[N:9]=[C:10]([CH3:12])[CH:11]=4)=[CH:3][C:2]=3[F:1])=[C:33]([C:43]#[N:44])[C:34]2=[O:42])[CH2:40][CH2:41]1

Participants

6

Reactant 3

HCID 516892Sodium BicarbonateHCID 59234229HCID 59234229, compoundHCID 59287324HCID 59287324, compound

Product 1

HCID 25003294HCID 25003294, compound

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Procedure

To a solution of intermediate 18 (1.05 mmol) in 1,4-dioxane (4.5 ml) and a saturated solution of NaHCO3 (4.5 ml) was added intermediate 5 (0.22 g, 0.892 mmol). The resulting solution was degassed using a stream of nitrogen and to this was added Pd(PPh3)4 (0.13 mg, 0.114 mmol). The reaction was then microwaved in a sealed tube at 150° C. for 10 minutes. The resulting cooled reaction mixture was filtered through a pad of diatomaceous earth. The filtrate was diluted with EtOAc, and then it was washed with water, dried over Na2SO4 and concentrated in vacuo. The crude reaction mixture was then purified by column chromatography (silica gel; DCM to DCM/MeOH up to 5% as eluent). The desired fractions were collected and evaporated in vacuo to give a residue that was further purified by column chromatography (silica gel; DCM to DCM/EtOAc up to 10% as eluent). The desired fractions were collected and evaporated in vacuo to yield compound 8 that was precipitated from diisopropylether (0.176 g, 51%).

Workup

  1. customThe resulting solution was degassed
  2. customThe reaction was then microwaved in a sealed tube at 150° C. for 10 minutes
  3. temperatureThe resulting cooled
  4. customreaction mixture
  5. filtrationwas filtered through a pad of diatomaceous earth
  6. additionThe filtrate was diluted with EtOAc
  7. washit was washed with water
  8. dry with materialdried over Na2SO4
  9. concentrationconcentrated in vacuo
  10. customThe crude reaction mixture
  11. customwas then purified by column chromatography (silica gel; DCM to DCM/MeOH up to 5% as eluent)
  12. customThe desired fractions were collected
  13. customevaporated in vacuo
  14. customto give a residue that
  15. customwas further purified by column chromatography (silica gel; DCM to DCM/EtOAc up to 10% as eluent)
  16. customThe desired fractions were collected
  17. customevaporated in vacuo

Sources & evidence

ORD record
ord-5fba05a574554aa09afb797b4a92df95
Source dataset
uspto-grants-2015_06
Patent number
US09067891B2

Reaction notes

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