4-(4-Bromophenylsulphonyl)-1-[2-(2,4-difluorophenyl)ethyl]piperidine → 1-[2-(2,4-Difluorophenyl)ethyl]-4-[4-(2-methyltetrazol-5-yl)-phenylsulphonyl]piperidine

HRID 411510

Reaction equation

HRID 411510 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([S:8]([CH:11]2[CH2:16][CH2:15][N:14]([CH2:17][CH2:18][C:19]3[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=3[F:26])[CH2:13][CH2:12]2)(=[O:10])=[O:9])=[CH:4][CH:3]=1.[CH3:27][N:28]1[N:32]=[N:31][C:30]([Sn](CCCC)(CCCC)CCCC)=[N:29]1.O.CCOC(C)=O>CN(C=O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[F:26][C:20]1[CH:21]=[C:22]([F:25])[CH:23]=[CH:24][C:19]=1[CH2:18][CH2:17][N:14]1[CH2:15][CH2:16][CH:11]([S:8]([C:5]2[CH:6]=[CH:7][C:2]([C:30]3[N:31]=[N:32][N:28]([CH3:27])[N:29]=3)=[CH:3][CH:4]=2)(=[O:10])=[O:9])[CH2:12][CH2:13]1

Participants

6

Reactant 3

HCID 110485124-(4-Bromophenylsulphonyl)-1-[2-(2,4-difluorophenyl)ethyl]piperidineHCID 225738832-methyl-5-(tributylstannyl)-2H-1,2,3,4-tetrazoleHCID 22728543Water ethylacetate

Product 1

HCID 234994851-[2-(2,4-Difluorophenyl)ethyl]-4-[4-(2-methyltetrazol-5-yl)-phenylsulphonyl]piperidineYield 57.2%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
110 °C

Procedure

A mixture of 4-(4-bromophenylsulphonyl)-1-[2-(2,4-difluorophenyl)ethyl]piperidine (0.38 g, 0.86 mmol), 2-methyl-5-(tributylstannyl)tetrazole (0.64 g, 1.72 mmol) and tetrakis(triphenylphosphine)palladium (100 mg, 0.02 mmol) in DMF was heated at 110° C. for 16 hours while stirring under nitrogen. The solution was poured into water/EtOAc (5/20 ml) and further extracted into EtOAc. The combined organic phase was washed with water, dried (Na2SO4) and evaporated to yield a syrup. Column chromatography (silica, EtOAc) followed by recrystallisation from EtOAc yielded 220 mg of crystalline material. δH (400 MHz, CDCl3) 1.73-1.80 (2H, m), 1.98-2.06 (4H, m), 2.50-2.54 (2H, m), 2.71-2.75 (2H, m), 2.92-2.98 (1H, m), 3.05-3.08 (2H, m), 4.45 (3H, s), 6.71-6.80 (2H, m), 7.09-7.14 (1H, m), 7.99 (1H, d, J 5.2 Hz), 8.34 (1H, d, J 5.2 Hz).

Workup

  1. extractionfurther extracted into EtOAc
  2. washThe combined organic phase was washed with water
  3. dry with materialdried (Na2SO4)
  4. customevaporated
  5. customto yield a syrup
  6. customColumn chromatography (silica, EtOAc) followed by recrystallisation from EtOAc

Sources & evidence

ORD record
ord-d3e71467081f47deab0bd32d6ef92758
Source dataset
uspto-grants-2003_05
Patent number
US06559166B1

Linked notes

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