Sodium Carbonate → HCID 89649316, compound

HRID 2207617Notes

Reaction equation

HRID 2207617 reaction equation
[CH2:1]([O:3][C:4]1[CH:5]=[CH:6][C:7]([F:13])=[C:8](B(O)O)[CH:9]=1)[CH3:2].[C:14](=O)([O-])[O-].[Na+].[Na+].Br[C:21]1[CH:26]=[CH:25][N:24]=[C:23]([C:27]2[CH2:31][CH2:30][C@@:29]3([CH2:35][CH2:34][N:33]([CH2:36][O:37][CH2:38][CH2:39][Si:40]([CH3:43])([CH3:42])[CH3:41])[C:32]3=[O:44])[N:28]=2)[CH:22]=1>C(COC)OC.O.C(Cl)Cl.C1(C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)[Pd][P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH2:1]([O:3][C:4]1[CH:5]=[CH:6][C:7]([F:13])=[C:8]([C:21]2[CH:26]=[CH:25][N:24]=[C:23]([C:27]3[CH2:31][CH2:30][C@:29]4([CH2:14][CH2:35][CH2:34][N:33]([CH2:36][O:37][CH2:38][CH2:39][Si:40]([CH3:43])([CH3:42])[CH3:41])[C:32]4=[O:44])[N:28]=3)[CH:22]=2)[CH:9]=1)[CH3:2]

Participants

8

Reactant 3

HCID 10340Sodium CarbonateHCID 162174685-Ethoxy-2-fluorophenylboronic Acid (contains varying amounts of Anhydride)HCID 89649320HCID 89649320, compound

Product 1

HCID 89649316HCID 89649316, compoundYield 82.2%

Reagents, catalysts & solvents 4

HCID 178419050HCID 178419050, compoundCatalystHCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 80711,2-DimethoxyethaneSolvent

Procedure

5-Ethoxy-2-fluorophenylboronic acid (129.98 mg, 0.7100 mmol) and sodium carbonate (213.96 mg, 2.02 mmol) were added to a solution of (5S)-2-(4-bromo-2-pyridyl)-7-(2-trimethylsilylethoxymethyl)-1,7-diazaspiro[4.4]non-1-en-6-one (which may be prepared as described in Description 47) (295 mg, 0.6700 mmol) in monoglyme (6 mL) and water (1.8 mL) under N2 at ambient temp. The mixture was degassed by bubbling N2 through it for 10 mins. Bis(triphenylphosphine)palladium (II) dichloride (23.62 mg, 0.0300 mmol) was then added and the stirred mixture was refluxed under N2 for 2.25 h. The reaction was cooled, diluted with DCM (40 ml) and the solution washed with water (40 ml), dried (MgSO4) and evaporated to a dark brown oil, which was dried at RT under vacuum for 2 hours. This was purified by SiO2 column chromatography: the oil was dissolved in DCM (3 ml) and the solution was applied to a 10 g cartridge which was then eluted on a Biotage SP4 system with a gradient of EtOAc/iso-hexane (20-100%). Relevant fractions were pooled and evaporated to a light brown oil, dried at RT under vacuum for 16 hours to afford (S)-2-[4-(5-ethoxy-2-fluoro-phenyl)-pyridin-2-yl]-7-(2-trimethylsilanyl-ethoxymethyl)-1,7-diaza-spiro[4.5]dec-1-en-6-one (D48) 274 mg;

Workup

  1. customThe mixture was degassed
  2. customby bubbling N2 through it for 10 mins
  3. temperaturethe stirred mixture was refluxed under N2 for 2.25 h
  4. temperatureThe reaction was cooled
  5. washthe solution washed with water (40 ml)
  6. dry with materialdried (MgSO4)
  7. customevaporated to a dark brown oil, which
  8. customwas dried at RT under vacuum for 2 hours
  9. customThis was purified by SiO2 column chromatography
  10. dissolutionthe oil was dissolved in DCM (3 ml)
  11. washwas then eluted on a Biotage SP4 system with a gradient of EtOAc/iso-hexane (20-100%)
  12. customevaporated to a light brown oil
  13. customdried at RT under vacuum for 16 hours

Sources & evidence

ORD record
ord-b2da2af4ed354dbfbfd47294c872dc54
Source dataset
uspto-grants-2016_06
Patent number
US09376436B2

Reaction notes

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