Lithium Hydroxide → HCID 66666008, compound

HRID 1617974Notes

Reaction equation

HRID 1617974 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([C@H:8]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=2[CH3:25])[CH2:9][C:10]([C:12]2[CH:17]=[CH:16][N:15]=[C:14]([CH3:18])[CH:13]=2)=[O:11])=[CH:4][CH:3]=1.[NH:26]1[CH2:31][CH2:30][CH:29]([C:32]([O:34]CC)=[O:33])[CH2:28][CH2:27]1.CC(C)([O-])C.[Na+].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1.[OH-].[Li+].S([O-])(O)(=O)=O.[K+].[Cl-].[NH4+]>C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].CO>[CH3:18][C:14]1[CH:13]=[C:12]([C:10](=[O:11])[CH2:9][C@H:8]([C:5]2[CH:4]=[CH:3][C:2]([N:26]3[CH2:31][CH2:30][CH:29]([C:32]([OH:34])=[O:33])[CH2:28][CH2:27]3)=[CH:7][CH:6]=2)[C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=2[CH3:25])[CH:17]=[CH:16][N:15]=1

Participants

11

Reactant 7

HCID 3939Lithium HydroxideHCID 25517Ammonium ChlorideHCID 70770Ethyl 4-piperidinecarboxylateHCID 516920Potassium bisulfateHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 23676156Sodium t-butoxideHCID 66666695(R)-3-(4-Bromo-phenyl)-1-(2-methyl-pyridin-4-yl)-3-o-tolyl-propan-1-one

Product 1

HCID 66666008HCID 66666008, compoundYield 99.8%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 887MethanolSolventHCID 1140TolueneSolvent

Conditions

Temperature
85 °C

Procedure

A mixture of (R)-3-(4-bromophenyl)-1-(2-methylpyridin-4-yl)-3-o-tolylpropan-1-one (example 142, step 2; 2.00 g, 5.07 mmol), ethyl piperidine-4-carboxylate (1.2 g, 7.61 mmol), sodium tert-butoxide (975 mg, 10.1 mmol), 2-dicyclohexylphosphino-2′,4′,6′-triisopropyl-biphenyl (484 mg, 1.01 mmol) and tris(dibenzylideneacetone)dipalladium(0) (464 mg, 507 μmol) in toluene (100 mL) was heated at 85° C. for 4 h and at room temperature for 17 h, then filtered through diatomaceous earth. After evaporation of volatile material, the residue was dissolved in tetrahydrofuran (50 mL), 1 M aq. lithium hydroxide solution (50 mL, 50 mmol) and methanol (15 mL), then after 2 h treated with 1 M aq. potassium hydrogensulfate solution (40 mL) and sat. aq. ammonium chloride solution (50 mL). The mixture was extracted with ethyl acetate, the organic layer washed with brine, dried over sodium sulfate, filtered, and evaporated. Chromatography (SiO2; dichloromethane-methanol gradient) produced the title compound (2.24 g, 66%). Light yellow solid, MS (ESI−): m/z=441.3 ([M−H]−).

Workup

  1. filtrationfiltered through diatomaceous earth
  2. customAfter evaporation of volatile material
  3. dissolutionthe residue was dissolved in tetrahydrofuran (50 mL)
  4. extractionThe mixture was extracted with ethyl acetate
  5. washthe organic layer washed with brine
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. customevaporated

Sources & evidence

ORD record
ord-bb4dc6980cf749c0bde4454e6b3ebf28
Source dataset
uspto-grants-2014_07
Patent number
US08765730B2

Reaction notes

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