Tetrahydrofuran → tert-Butyl 4-hydroxy-4-(4-(trifluoromethoxy)phenyl)piperidine-1-carboxylate

HRID 1043528Notes

Reaction equation

HRID 1043528 reaction equation
[F:1][C:2]([F:12])([F:11])[O:3][C:4]1[CH:9]=[CH:8][C:7](Br)=[CH:6][CH:5]=1.C([Li])CCC.[C:18]([O:22][C:23]([N:25]1[CH2:30][CH2:29][C:28](=C=O)[CH2:27][CH2:26]1)=[O:24])([CH3:21])([CH3:20])[CH3:19].[Cl-].[NH4+].[O:35]1CCCC1>>[C:18]([O:22][C:23]([N:25]1[CH2:30][CH2:29][C:28]([OH:35])([C:7]2[CH:8]=[CH:9][C:4]([O:3][C:2]([F:12])([F:11])[F:1])=[CH:5][CH:6]=2)[CH2:27][CH2:26]1)=[O:24])([CH3:21])([CH3:20])[CH3:19]

Participants

6

Reactant 5

HCID 8028Tetrahydrofuran2×HCID 25517Ammonium ChlorideHCID 5210081-Bromo-4-(trifluoromethoxy)benzeneHCID 866859024-Carbonyl piperidine-1-formic acid tert-butyl esterHCID 178418339Butyllithium

Product 1

HCID 68626953tert-Butyl 4-hydroxy-4-(4-(trifluoromethoxy)phenyl)piperidine-1-carboxylateYield 40%

Conditions

Temperature
-78 °C

Procedure

4-trifluoromethoxy bromobenzene (2.41 g, 10 mmol) was dissolved in dry tetrahydrofuran (30 mL), cooled to −78° C., to which slowly added dropwise n-butyllithium (1.6M n-hexane solution, 6.5 mL), kept the temperature below −70° C. during the dropwise adding procedure, after adding, kept stirring this system for 20 min, added 4-carbonyl piperidine-1-formic acid tert-butyl ester (1.99 g, 10 mmol) in tetrahydrofuran solution, kept the temperature below −70° C. during the dropwise adding procedure, after adding, the temperature can be increased to room temperature while stirring for 15 h. After the reaction was finished, added saturated ammonium chloride aqueous solution to quench reaction, partitioned, organic phases were washed by saturated saline, followed by anhydrous sodium sulphate drying, concentration, column chromatography (PE: EA=15:1) to give 1.6 g light yellow gel-like substance, yield: 40%.

Workup

  1. customthe temperature below −70° C.
  2. additiondropwise adding procedure
  3. additionafter adding
  4. customthe temperature below −70° C.
  5. additiondropwise adding procedure
  6. additionafter adding
  7. temperaturethe temperature can be increased to room temperature
  8. stirringwhile stirring for 15 h
  9. customto quench
  10. customreaction
  11. custompartitioned
  12. washorganic phases were washed by saturated saline
  13. concentrationfollowed by anhydrous sodium sulphate drying, concentration, column chromatography (PE: EA=15:1)
  14. customto give 1.6 g light yellow gel-like substance, yield: 40%

Sources & evidence

ORD record
ord-c7b0aadc8915427cad1626b1ab110b2c
Source dataset
uspto-grants-2013_10
Patent number
US08563547B2

Reaction notes

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