Sodium Carbonate → tert-Butyl 4-(phenyl(3-(5-(trifluoromethyl)pyridin-2-yloxy)phenyl)methylene)piperidine-1-carboxylate

HRID 1666481Notes

Reaction equation

HRID 1666481 reaction equation
Br[C:2]([C:16]1[CH:21]=[CH:20][CH:19]=[C:18]([O:22][C:23]2[CH:28]=[CH:27][C:26]([C:29]([F:32])([F:31])[F:30])=[CH:25][N:24]=2)[CH:17]=1)=[C:3]1[CH2:8][CH2:7][N:6]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:5][CH2:4]1.[C:33]1(B(O)O)[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1.C([O-])([O-])=O.[Na+].[Na+]>C1(C)C=CC=CC=1.C(O)C>[C:33]1([C:2]([C:16]2[CH:21]=[CH:20][CH:19]=[C:18]([O:22][C:23]3[CH:28]=[CH:27][C:26]([C:29]([F:31])([F:32])[F:30])=[CH:25][N:24]=3)[CH:17]=2)=[C:3]2[CH2:4][CH2:5][N:6]([C:9]([O:11][C:12]([CH3:15])([CH3:13])[CH3:14])=[O:10])[CH2:7][CH2:8]2)[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 66827Phenylboronic AcidHCID 66876318Tert-butyl 4-(bromo(3-(5-(trifluoromethyl)pyridin-2-yloxy)phenyl)methylene)piperidine-1-carboxylate

Product 1

HCID 67445311tert-Butyl 4-(phenyl(3-(5-(trifluoromethyl)pyridin-2-yloxy)phenyl)methylene)piperidine-1-carboxylateYield 66%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 1140TolueneSolvent

Conditions

Temperature
90 °C

Procedure

To a solution of tert-butyl 4-(bromo(3-(5-(trifluoromethyl)pyridin-2-yloxy)phenyl)methylene)piperidine-1-carboxylate (Example 71, Step 2) (91 mg, 0.18 mmol) in anhydrous toluene (3 mL) and ethanol (3 mL) was added phenyl boronic acid (43.7 mg, 0.358 mmol) and 2M Na2CO3 (0.53 mL, 1.08 mmol). This solution was degassed for 20 min and Pd(PPh3)4 (19 mg, 10 mol %) was added. The reaction was heated at 90° C. overnight. The reaction was cooled and extracted with EtOAc (3×). The organic layer was dried over MgSO4 and concentrated. Purification by silica gel column chromatography (0-5% MeOH/CH2Cl2) gave the title compound as a foam (60 mg, 66% yield).

Workup

  1. customThis solution was degassed for 20 min
  2. additionPd(PPh3)4 (19 mg, 10 mol %) was added
  3. temperatureThe reaction was cooled
  4. extractionextracted with EtOAc (3×)
  5. dry with materialThe organic layer was dried over MgSO4
  6. concentrationconcentrated
  7. customPurification by silica gel column chromatography (0-5% MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-e25638ca568e49fe9dd281b29250f916
Source dataset
uspto-grants-2011_10
Patent number
US08044052B2

Reaction notes

Loading…