Potassium Phosphate, Tribasic → tert-Butyl 4-(3-(5-cyclopropylpyridin-2-yloxy)benzylidene)piperidine-1-carboxylate

HRID 1666383Notes

Reaction equation

HRID 1666383 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([O:8][C:9]2[CH:10]=[C:11]([CH:26]=[CH:27][CH:28]=2)[CH:12]=[C:13]2[CH2:18][CH2:17][N:16]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:15][CH2:14]2)=[N:6][CH:7]=1.[CH:29]1(B(O)O)[CH2:31][CH2:30]1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].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[CH:3]=[CH:4][C:5]([O:8][C:9]3[CH:10]=[C:11]([CH:26]=[CH:27][CH:28]=3)[CH:12]=[C:13]3[CH2:18][CH2:17][N:16]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:15][CH2:14]3)=[N:6][CH:7]=2)[CH2:31][CH2:30]1

Participants

8

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 75806TricyclohexylphosphineHCID 2760897Cyclopropylboronic acidHCID 66876348tert-Butyl 4-(3-(5-bromopyridin-2-yloxy)benzylidene)piperidine-1-carboxylate

Product 1

HCID 66876584tert-Butyl 4-(3-(5-cyclopropylpyridin-2-yloxy)benzylidene)piperidine-1-carboxylateYield 87%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolvent2×HCID 1140TolueneSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of tert-butyl 4-(3-(5-bromopyridin-2-yloxy)benzylidene)piperidine-1-carboxylate (Example 33, step 4) (1.64 g, 3.68 mmol) in toluene (12 mL) and water (0.6 mL) under a N2 atmosphere was added cyclopropyl boronic acid (410 mg, 4.77 mmol), potassium phosphate (2.24 g, 12.9 mmol), tricyclohexyl phosphine (103 mg, 0.367 mmol) and palladium acetate (41.2 mg, 0.184 mmol). The mixture was heated at 80° C. overnight. The reaction was cooled to RT and water was added. The mixture was extracted with ethyl acetate and the organic layer was washed with brine, dried over MgSO4 and concentrated. Purification by silica gel column chromatography (0-50% EtOAc/hexane) gave the title compound as an oil that solidified on the vacuum pump (1.3 g, 87% yield).

Workup

  1. temperatureThe reaction was cooled to RT
  2. extractionThe mixture was extracted with ethyl acetate
  3. washthe organic layer was washed with brine
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated
  6. customPurification by silica gel column chromatography (0-50% EtOAc/hexane)

Sources & evidence

ORD record
ord-f4fde6862a0b4af8b2cd457bcb3f481c
Source dataset
uspto-grants-2011_10
Patent number
US08044052B2

Reaction notes

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