Cesium carbonate → Tert-butyl({1-[4-(trifluoromethyl)phenyl]piperidin-4-yl}methyl)carbamate

HRID 1047387Notes

Reaction equation

HRID 1047387 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]([F:11])([F:10])[F:9])=[CH:4][CH:3]=1.[C:12]([O:16][C:17](=[O:26])[NH:18][CH2:19][CH:20]1[CH2:25][CH2:24][NH:23][CH2:22][CH2:21]1)([CH3:15])([CH3:14])[CH3:13].C(=O)([O-])[O-].[Cs+].[Cs+].C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>O1CCOCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O>[C:12]([O:16][C:17](=[O:26])[NH:18][CH2:19][CH:20]1[CH2:21][CH2:22][N:23]([C:2]2[CH:7]=[CH:6][C:5]([C:8]([F:11])([F:10])[F:9])=[CH:4][CH:3]=2)[CH2:24][CH2:25]1)([CH3:15])([CH3:13])[CH3:14]

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 67872Benzene, 1-bromo-4-(trifluoromethyl)-HCID 634876Binap, (A+-)-HCID 723429Tert-butyl (piperidin-4-ylmethyl)carbamate

Product 1

HCID 66853254Tert-butyl({1-[4-(trifluoromethyl)phenyl]piperidin-4-yl}methyl)carbamateYield 61.8%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent2×

Conditions

Temperature
110 °C

Procedure

A solution of 1-bromo-4-trifluoromethyl-benzene (50.0 g; 220 mmol) and piperidin-4-ylmethyl-carbamic acid tert-butyl ester (48.1 g; 220 mmol) in dioxane (1 L) was added to a suspension of palladium (II) acetate (7.41 g; 33 mmol), cesium carbonate (144.8 g; 440 mmol), and 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (31.8 g; 45 mmol) in dioxane (1 L). The resulting mixture was heated to 110° C., and then maintained at that temperature for 28 hr with stirring. The mixture was then allowed to cool to room temperature. Afterward, the reaction mixture was treated with water (2 L) and extracted with dichloromethane (2×1 L). The combined organic phases were dried over sodium sulfate and filtered, and then the solvents were removed under reduced pressure. The resulting residue was dissolved in acetonitrile (1.5 L). Water (1.5 L) was then added with stirring. This resulting in a precipitate, which was filtered and then dried overnight at 40° C. at a pressure of 3 mbar to afford the desired product (48.9 g; 136 mmol).

Workup

  1. temperaturemaintained at that temperature for 28 hr
  2. temperatureto cool to room temperature
  3. extractionextracted with dichloromethane (2×1 L)
  4. dry with materialThe combined organic phases were dried over sodium sulfate
  5. filtrationfiltered
  6. customthe solvents were removed under reduced pressure
  7. dissolutionThe resulting residue was dissolved in acetonitrile (1.5 L)
  8. additionWater (1.5 L) was then added
  9. stirringwith stirring
  10. filtrationThis resulting in a precipitate, which was filtered
  11. customdried overnight at 40° C. at a pressure of 3 mbar

Sources & evidence

ORD record
ord-5b410fe0dc6541578101b8c64bdb4448
Source dataset
uspto-grants-2013_10
Patent number
US08569495B2

Reaction notes

Loading…