Benzenesulfonyl chloride → 4-[2-(1-Benzenesulfonyl-piperidin-3-yloxy)-phenyl]-piperazine-1-carboxylic acid tert-butyl ester

HRID 456463Notes

Reaction equation

HRID 456463 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=2[O:20][CH:21]2[CH2:26][CH2:25][CH2:24][N:23](C(OCC3C=CC=CC=3)=O)[CH2:22]2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[H][H].C(N(CC)CC)C.[C:46]1([S:52](Cl)(=[O:54])=[O:53])[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=1>CO.[Pd].C(OCC)(=O)C.C(Cl)Cl>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=2[O:20][CH:21]2[CH2:26][CH2:25][CH2:24][N:23]([S:52]([C:46]3[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=3)(=[O:54])=[O:53])[CH2:22]2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

9

Reactant 4

HCID 7369Benzenesulfonyl chlorideHCID 8471Triethylamine2×HCID 694231604-[2-(1-Benzyloxycarbonyl-piperidin-3-yloxy)-phenyl]-piperazine-1-carboxylic acid tert-butyl esterHCID 178418361HCID 178418361, compound

Product 1

HCID 694221304-[2-(1-Benzenesulfonyl-piperidin-3-yloxy)-phenyl]-piperazine-1-carboxylic acid tert-butyl esterYield 82%

Reagents, catalysts & solvents 4

HCID 23938PalladiumCatalystHCID 887MethanolSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent2×

Procedure

The compound of Step 1 (2.5 g, 4.7 mmol) was dissolved in methanol (20 mL). Palladium on carbon (50% water, 2.1 g) was added. A hydrogen atmosphere was established using balloons, and the mixture was stirred at r.t. for about 4 hours. The catalyst was removed by filtration with ethyl acetate through a bed of celite. The compound was isolated by running scrub-plug with a gradient of 100% ethyl acetate (200 mL) to triethylamine in ethyl acetate (10%). The isolated product (0.36 g, 0.9 mmol) was dissolved in methylene chloride (10 mL) at 0° C., and triethylamine (0.38 mL, 2.7 mmol) was added. Benzenesulfonyl chloride (0.15 mL, 1.1 mmol) was added drop wise to the reaction mixture. The solution warmed to r.t., concentrated under reduced pressure and purified using silica gel chromatography (75% ethyl acetate in hexanes) to afford the final compound (0.400 g, 82%).

Workup

  1. customThe catalyst was removed by filtration with ethyl acetate through a bed of celite
  2. customThe compound was isolated
  3. temperatureThe solution warmed to r.t.
  4. concentrationconcentrated under reduced pressure
  5. custompurified

Sources & evidence

ORD record
ord-c30e056c1f274e40a6386fd36084f046
Source dataset
uspto-grants-2007_03
Patent number
US07186715B2

Reaction notes

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