Trimethylamine oxide → HCID 16103024, compound

HRID 1786300Notes

Reaction equation

HRID 1786300 reaction equation
C12BC(CCC1)CCC2.O1CCCC1.[CH2:15]([OH:19])[CH2:16][CH:17]=[CH2:18].[F:20][C:21]1[CH:26]=[C:25](OS(C(F)(F)F)(=O)=O)[CH:24]=[C:23]([F:35])[C:22]=1[CH:36]([C:42]([O:44][CH2:45][CH3:46])=[O:43])[C:37]([O:39][CH2:40][CH3:41])=[O:38].P([O-])([O-])([O-])=O.[K+].[K+].[K+].C[N+]([O-])(C)C>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.C(OCC)(=O)C>[F:20][C:21]1[CH:26]=[C:25]([CH2:18][CH2:17][CH2:16][CH2:15][OH:19])[CH:24]=[C:23]([F:35])[C:22]=1[CH:36]([C:42]([O:44][CH2:45][CH3:46])=[O:43])[C:37]([O:39][CH2:40][CH3:41])=[O:38]

Participants

10

Reactant 6

HCID 1145Trimethylamine oxideHCID 8028TetrahydrofuranHCID 62657Potassium Phosphate, TribasicHCID 693893-Buten-1-olHCID 789669-Borabicyclo(3.3.1)nonaneHCID 16103032HCID 16103032, compound

Product 1

HCID 16103024HCID 16103024, compoundYield 42.7%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Procedure

To a 0.5 M solution of 9-borabicyclo[3.3.1]nonane (9-BBN) in tetrahydrofuran (95 mL, 47.6 mmol) is added dropwise 3-butene-1-ol (4.1 mL, 47.6 mmol), and the mixture is stirred under nitrogen atmosphere at room temperature for 6 h. The resulting solution is then transferred by a double-ended needle into a mixture of diethyl 2-(2,6-difluoro-4-{[(trifluoromethyl)sulfonyl]oxy}phenyl)malonate (10.0 g, 23.8 mmol), potassium phosphate (10.1 g, 47.6 mmol), and tetrakis(triphenylphosphine)palladium(0) (825 mg, 0.714 mmol) in 40 mL of dioxane under nitrogen pressure. The mixture is then heated at 90° C. for 8 h. The reaction is cooled to room temperature, and trimethylamine-N-oxide (3.57 g, 47.6 mmol) is added. The reaction is heated at 80° C. for 1 h and cooled to room temperature. Ethyl acetate is added to dilute the reaction. The organic phase is washed with saturated sodium chloride (x2), dried over magnesium sulfate, and concentrated to a residue. The residue is chromatographed over silica gel, eluting with a gradient of 10% ethyl acetate in hexanes to 50% ethyl acetate in hexanes. Concentration provides diethyl 2-[2,6-difluoro-4-(4-hydroxybutyl)phenyl]malonate as a brown oil (3.5 g). MS: m/z 345.2 (M+H).

Workup

  1. temperatureThe mixture is then heated at 90° C. for 8 h
  2. temperatureThe reaction is cooled to room temperature
  3. temperatureThe reaction is heated at 80° C. for 1 h
  4. temperaturecooled to room temperature
  5. additionto dilute
  6. customthe reaction
  7. washThe organic phase is washed with saturated sodium chloride (x2)
  8. dry with materialdried over magnesium sulfate
  9. concentrationconcentrated to a residue
  10. customThe residue is chromatographed over silica gel
  11. washeluting with a gradient of 10% ethyl acetate in hexanes to 50% ethyl acetate in hexanes
  12. concentrationConcentration

Sources & evidence

ORD record
ord-9d939f4404c241e5b2b77e09326f51eb
Source dataset
uspto-grants-2009_03
Patent number
US07507739B2

Reaction notes

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