Benzaldehyde → 1-Benzyl-4-[(4-chlorophenyl)sulfonyl]-4-(2,5-difluorophenyl)piperidine

HRID 748804Notes

Reaction equation

HRID 748804 reaction equation
Cl.[Cl:2][C:3]1[CH:8]=[CH:7][C:6]([S:9]([C:12]2([C:18]3[CH:23]=[C:22]([F:24])[CH:21]=[CH:20][C:19]=3[F:25])[CH2:17][CH2:16][NH:15][CH2:14][CH2:13]2)(=[O:11])=[O:10])=[CH:5][CH:4]=1.C(N(CC)CC)C.[CH:33](=O)[C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[OH-].[Na+]>CO.ClCCl.C(OCC)C>[CH2:33]([N:15]1[CH2:16][CH2:17][C:12]([S:9]([C:6]2[CH:7]=[CH:8][C:3]([Cl:2])=[CH:4][CH:5]=2)(=[O:10])=[O:11])([C:18]2[CH:23]=[C:22]([F:24])[CH:21]=[CH:20][C:19]=2[F:25])[CH2:13][CH2:14]1)[C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1

Participants

9

Reactant 5

HCID 240BenzaldehydeHCID 8471TriethylamineHCID 14798Sodium HydroxideHCID 5049666Sodium triacetoxyborohydrideHCID 692029464-[(4-Chlorophenyl)sulfonyl]-4-(2,5-difluorophenyl)piperidine Hydrochloride

Product 1

HCID 597507261-Benzyl-4-[(4-chlorophenyl)sulfonyl]-4-(2,5-difluorophenyl)piperidineYield 77.6%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolvent2×

Procedure

The 4-[(4-chlorophenyl)sulfonyl]-4-(2,5-difluorophenyl)piperidine hydrochloride (100 mg, 0.245 mmol) obtained in Example 260, triethylamine (0.070 ml, 0.50 mmol) and benzaldehyde (0.050 ml, 0.428 mmol) were added to dichloromethane (5 ml), followed by the addition of sodium triacetoxyborohydride (110 mg, 0.500 mmol) at room temperature. The resulting mixture was stirred at room temperature for 14 hours. A 1N aqueous sodium hydroxide solution (3.0 ml) was then added. The resulting mixture was stirred at room temperature for 30 minutes. After diethyl ether was added, the resulting mixture was washed with a 1N aqueous sodium hydroxide solution. The organic layer was dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure. The residue thus obtained was subjected to flash silica gel chromatography, and the fraction obtained from the dichloromethane:methanol=50:1 eluate was concentrated under reduced pressure, whereby the title compound (87 mg, 0.19 mmol, 77%) was obtained as a white foam.

Workup

  1. stirringThe resulting mixture was stirred at room temperature for 30 minutes
  2. washthe resulting mixture was washed with a 1N aqueous sodium hydroxide solution
  3. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  4. filtrationAfter filtration
  5. concentrationthe filtrate was concentrated under reduced pressure
  6. customThe residue thus obtained

Sources & evidence

ORD record
ord-29d67c405595431d8ef396e501be29fc
Source dataset
uspto-grants-2008_07
Patent number
US07399775B2

Reaction notes

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