Potassium Phosphate, Tribasic → HCID 86703557, compound

HRID 1849686Notes

Reaction equation

HRID 1849686 reaction equation
Cl[C:2]1[C:3]([O:16][CH2:17][C:18]2([CH3:28])[CH2:27][CH2:26][C:21]3([O:25][CH2:24][CH2:23][O:22]3)[CH2:20][CH2:19]2)=[CH:4][C:5]([F:15])=[C:6]([CH:14]=1)[C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8].[CH:29]1(B(O)O)[CH2:31][CH2:30]1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].F[B-](F)(F)F.C1(P(C2CCCCC2)C2CCCCC2)CCCCC1>C1(C)C=CC=CC=1.O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH:29]1([C:2]2[C:3]([O:16][CH2:17][C:18]3([CH3:28])[CH2:19][CH2:20][C:21]4([O:22][CH2:23][CH2:24][O:25]4)[CH2:26][CH2:27]3)=[CH:4][C:5]([F:15])=[C:6]([CH:14]=2)[C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[CH2:31][CH2:30]1

Participants

8

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 2760897Cyclopropylboronic acidHCID 20066521Tri(cyclohexyl)phosphine tetrafluoroborateHCID 86703556HCID 86703556, compound

Product 1

HCID 86703557HCID 86703557, compoundYield 83%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of tert-butyl 5-chloro-2-fluoro-4-((8-methyl-1,4-dioxaspiro[4.5]decan-8-yl)methoxy)benzoate (3.09 g, 7.45 mmol), cyclopropylboronic acid (0.96 g, 11.17 mmol), potassium phosphate (7.12 g, 33.53 mmol) and tricyclohexylphosphine tetrafluoroborate (0.28 g, 0.75 mmol) in toluene (50 mL) and water (2.5 mL). The resulting suspension was sparged with Argon for 15 minutes before the addition of palladium acetate (0.083 g, 0.37 mmol). The reaction mixture was heated at 100° C. for 18 hours and then cooled to ambient temperature; filtered through a pad of diatomaceous earth and rinsed with ethyl acetate. The filtrate was diluted with additional water (20 mL). The organic layer was separated, washed with brine, dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was filtered through a plug of silica gel (100% ethyl acetate) to afford the title compound (2.59 g, 83%) as a colorless oil: MS (ES+) m/z 365.2 (M−55).

Workup

  1. temperaturecooled to ambient temperature
  2. filtrationfiltered through a pad of diatomaceous earth
  3. washrinsed with ethyl acetate
  4. additionThe filtrate was diluted with additional water (20 mL)
  5. customThe organic layer was separated
  6. washwashed with brine
  7. dry with materialdried over anhydrous sodium sulfate
  8. concentrationconcentrated in vacuo
  9. filtrationThe residue was filtered through a plug of silica gel (100% ethyl acetate)

Sources & evidence

ORD record
ord-903b07897ad2465191c2960c8d7eaed1
Source dataset
uspto-grants-2015_02
Patent number
US08952169B2

Reaction notes

Loading…