Hydrochloric Acid → 6-Hydroxy-1-(4-(2-(piperidin-1-yl)ethoxy)phenoxy)naphthalen-2-ylboronic acid hydrochloride

HRID 445220Notes

Reaction equation

HRID 445220 reaction equation
[B:1]1(B2OCC(C)(C)CO2)[O:6]CC(C)(C)C[O:2]1.C([O:20][C:21]1[CH:30]=[CH:29][C:28]2[C:23](=[CH:24][CH:25]=[C:26](OS(C(F)(F)F)(=O)=O)[C:27]=2[O:31][C:32]2[CH:37]=[CH:36][C:35]([O:38][CH2:39][CH2:40][N:41]3[CH2:46][CH2:45][CH2:44][CH2:43][CH2:42]3)=[CH:34][CH:33]=2)[CH:22]=1)(=O)C.[F-].[Cs+].C1(P(C2CCCCC2)C2CCCCC2)CCCCC1.N(CCO)CCO.[ClH:83]>CCOCC.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C(#N)C>[ClH:83].[OH:20][C:21]1[CH:22]=[C:23]2[C:28](=[CH:29][CH:30]=1)[C:27]([O:31][C:32]1[CH:37]=[CH:36][C:35]([O:38][CH2:39][CH2:40][N:41]3[CH2:46][CH2:45][CH2:44][CH2:43][CH2:42]3)=[CH:34][CH:33]=1)=[C:26]([B:1]([OH:6])[OH:2])[CH:25]=[CH:24]2

Participants

10

Reactant 6

HCID 313Hydrochloric AcidHCID 8113DiethanolamineHCID 25953Cesium fluorideHCID 75806TricyclohexylphosphineHCID 2734316Bis(neopentyl glycolato)diboronHCID 583385445-(4-(2-(Piperidin-1-yl)ethoxy)phenoxy)-6-(trifluoromethylsulfonyloxy)naphthalen-2-yl acetate

Product 1

HCID 673086676-Hydroxy-1-(4-(2-(piperidin-1-yl)ethoxy)phenoxy)naphthalen-2-ylboronic acid hydrochloride

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 3283Diethyl EtherSolventHCID 6342AcetonitrileSolvent

Procedure

Add bis(neopentyl glycolato)diboron (4.2 g, 18.59 mmol), 5-(4-(2-(piperidin-1-yl)ethoxy)phenoxy)-6-(trifluoromethylsulfonyloxy)naphthalen-2-yl acetate (2.33 g, 4.21 mmol), palladium (II) acetate (0.199 g, 886.38 μmol), cesium fluoride (5.21 g, 34.30 mmol), tricyclohexylphosphine (0.41 g, 1.40 mmol) and acetonitrile (50 mL) to a round bottom flask. Reflux the mixture with stirring for 1 hour under a nitrogen atmosphere. Cool the mixture, filter and wash the solids with acetonitrile. Concentrate the combined filtrate and washes. Suspend the resulting residue in diethyl ether (40 mL) and sonicated for 30 minutes. Remove the precipitate by filtration and concentrate the filtrate to obtain the crude intermediate. Add diethanolamine (405.25 μL, 4.21 mmol) to a solution of the crude intermediate in ether (50 mL). Stir the mixture for 1 hour. Decant the organic layer and dissolve the remaining residue in methanol (20 mL) and 10 mL of water. Add concentrated HCl (2 mL; 24 mmol) and stir the resulting mixture for 16 hours. Concentrate the mixture to remove MeOH. Extract the aqueous residue 3 times with dichloromethane. Combine the extracts, dry over sodium sulfate, filter, and concentrate to dryness. Purify the residue by flash chromatography on silica to obtain the title compound. (0.6 g, 1.47 mmol).

Workup

  1. temperatureReflux the mixture
  2. temperatureCool the mixture
  3. filtrationfilter
  4. washwash the solids with acetonitrile
  5. concentrationConcentrate the combined filtrate and washes
  6. customsonicated for 30 minutes
  7. customRemove the precipitate
  8. filtrationby filtration
  9. concentrationconcentrate the filtrate
  10. customto obtain the crude intermediate
  11. stirringStir the mixture for 1 hour
  12. customDecant the organic layer
  13. dissolutiondissolve the remaining residue in methanol (20 mL)
  14. stirringstir the resulting mixture for 16 hours
  15. concentrationConcentrate the mixture
  16. customto remove MeOH
  17. extractionExtract the aqueous residue 3 times with dichloromethane
  18. dry with materialdry over sodium sulfate
  19. filtrationfilter
  20. concentrationconcentrate to dryness
  21. customPurify the residue by flash chromatography on silica

Sources & evidence

ORD record
ord-064303eb94814fe7997246c3d8d2de75
Source dataset
uspto-grants-2013_07
Patent number
US08476300B2

Reaction notes

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