Bromide ion → HCID 15390162, compound

HRID 378501Notes

Reaction equation

HRID 378501 reaction equation
[Mg].[F:2][C:3]([F:13])([F:12])[O:4][C:5]1[CH:10]=[CH:9][C:8](Br)=[CH:7][CH:6]=1.[Br-].[CH3:15][O:16][C:17]1[CH:22]=[CH:21][C:20]([CH2:23][N:24]2[CH2:29][CH2:28][CH:27]([C:30]([O:32]CC)=O)[CH2:26][CH2:25]2)=[CH:19][CH:18]=1.[Cl-].[NH4+]>C(OCC)C>[CH3:15][O:16][C:17]1[CH:18]=[CH:19][C:20]([CH2:23][N:24]2[CH2:25][CH2:26][CH:27]([C:30]([C:8]3[CH:7]=[CH:6][C:5]([O:4][C:3]([F:2])([F:12])[F:13])=[CH:10][CH:9]=3)([C:8]3[CH:9]=[CH:10][C:5]([O:4][C:3]([F:13])([F:12])[F:2])=[CH:6][CH:7]=3)[OH:32])[CH2:28][CH2:29]2)=[CH:21][CH:22]=1

Participants

7

Reactant 5

HCID 259Bromide ionHCID 25517Ammonium ChlorideHCID 5210081-Bromo-4-(trifluoromethoxy)benzeneHCID 765963HCID 765963, compoundHCID 5462224Magnesium

Product 1

HCID 15390162HCID 15390162, compoundYield 67%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent3×

Procedure

To a stirred mixture of 1.1 grams (0.045 gram-atom) of magnesium turnings in 30 mL of diethyl ether was added dropwise 15 mL of a solution of 11.0 grams (0.045 mole) of 4-trifluoromethoxyphenyl bromide in 30 mL of diethyl ether. Once the reaction had started, the remaining 15 mL of the bromide solution was added portionwise during a 45 minute period. When the reaction subsided, a solution of 5.0 grams (0.018 mole) of ethyl N-(4-methoxyphenylmethyl)piperidin-4-ylcarboxylate in 20 mL of diethyl ether was added dropwise during a five minute period. Upon completion of the addition, the reaction mixture was heated to reflux, where it stirred for about 30 minutes. The reaction mixture was then allowed to cool to ambient temperature, where it stirred for about 18 hours. After this time an aqueous solution saturated with ammonium chloride was added dropwise to quench the reaction. The mixture was then partitioned between water and diethyl ether. The diethyl ether layer was separated and washed first with a solution saturated with sodium chloride and then with water. The organic layer was dried with magnesium sulfate and filtered. The filtrate was concentrated under reduced pressure to a residual oil. The oil was subjected to column chromatography on silica gel, with 10% diethyl ether in hexane, 100% diethyl ether, and 10% methanol in diethyl ether as eluants. The product-containing fractions were combined and concentrated under reduced pressure, yielding 6.7 grams of N-(4-methoxyphenylmethyl)-4-[bis(4-trifluoromethoxyphenyl)hydroxymethyl]piperidine, mp 86-96° C. The NMR spectrum was consistent with the proposed structure.

Workup

  1. additionUpon completion of the addition
  2. temperaturethe reaction mixture was heated
  3. temperatureto reflux
  4. stirringwhere it stirred for about 18 hours
  5. customto quench
  6. customthe reaction
  7. customThe mixture was then partitioned between water and diethyl ether
  8. customThe diethyl ether layer was separated
  9. washwashed first with a solution saturated with sodium chloride
  10. dry with materialThe organic layer was dried with magnesium sulfate
  11. filtrationfiltered
  12. concentrationThe filtrate was concentrated under reduced pressure to a residual oil
  13. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-9d8d39ba6f55439c8e2c5e1fc875d176
Source dataset
uspto-grants-2000_02
Patent number
US06030987

Reaction notes

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