1-Bromo-4-(trifluoromethoxy)benzene → N-(4-fluoroindol-3-ylmethyl)-4-[bis(4-trifluoromethoxyphenyl)hydroxymethyl]piperidine

HRID 1683860Notes

Reaction equation

HRID 1683860 reaction equation
[F:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[C:4]([CH2:11][N:12]1[CH2:17][CH2:16][CH:15]([C:18]([O:20]CC)=O)[CH2:14][CH2:13]1)=[CH:5][NH:6]2.[F:23][C:24]([F:34])([F:33])[O:25][C:26]1[CH:31]=[CH:30][C:29](Br)=[CH:28][CH:27]=1.[Mg]>C(OCC)C.CCCCCC>[F:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[C:4]([CH2:11][N:12]1[CH2:13][CH2:14][CH:15]([C:18]([C:29]3[CH:28]=[CH:27][C:26]([O:25][C:24]([F:23])([F:33])[F:34])=[CH:31][CH:30]=3)([C:29]3[CH:30]=[CH:31][C:26]([O:25][C:24]([F:34])([F:33])[F:23])=[CH:27][CH:28]=3)[OH:20])[CH2:16][CH2:17]1)=[CH:5][NH:6]2

Participants

6

Reactant 3

HCID 5210081-Bromo-4-(trifluoromethoxy)benzeneHCID 5462224MagnesiumHCID 19040931ethyl N-(4-fluoroindol-3-ylmethyl)piperidin-4-ylcarboxylate

Product 1

HCID 19040930N-(4-fluoroindol-3-ylmethyl)-4-[bis(4-trifluoromethoxyphenyl)hydroxymethyl]piperidineYield 9.7%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8058HexaneSolvent

Procedure

This compound was prepared in a manner analogous to that of Step B of Example 3, with 0.5 gram (0.0016 mole) of ethyl N-(4-fluoroindol-3-ylmethyl)piperidin-4-ylcarboxylate, 2.0 grams (0.0082 mole) of 4-trifluoromethoxyphenyl bromide, and 0.2 gram (0.0086 gram-atom) of magnesium turnings in about 10 mL of diethyl ether as reagents. The crude reaction product was taken up in hexane. The hexane-insoluble material was collected by filtration and purified by preparative thin layer chromatography with 1:3 ethyl acetate:hexane as an eluant, yielding about 0.09 gram of N-(4-fluoroindol-3-ylmethyl)-4-[bis(4-trifluoromethoxyphenyl)hydroxymethyl]piperidine, mp 76°-88° C. The NMR spectrum was consistent with the proposed structure.

Workup

  1. customThis compound was prepared in a manner analogous to that of Step B of Example 3
  2. customThe crude reaction product
  3. filtrationThe hexane-insoluble material was collected by filtration
  4. custompurified by preparative thin layer chromatography with 1:3 ethyl acetate

Sources & evidence

ORD record
ord-db709b404ebe4f8bb374c6f7f15f0215
Source dataset
uspto-grants-1997_06
Patent number
US05639763

Reaction notes

Loading…