Triethylamine → 4-{2-[1-(Propane-2-sulfonyl)-piperidin-3-yloxy]-phenyl}-piperazine-1-carboxylic acid tert-butyl ester

HRID 456459Notes

Reaction equation

HRID 456459 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.[CH:46]([S:49](Cl)(=[O:51])=[O:50])([CH3:48])[CH3:47]>CO.[Pd].C(OCC)(=O)C.C(Cl)Cl>[C:1]([O:5][C:6]([N:8]1[CH2:9][CH2:10][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:49]([CH:46]([CH3:48])[CH3:47])(=[O:51])=[O:50])[CH2:22]2)[CH2:12][CH2:13]1)=[O:7])([CH3:3])([CH3:2])[CH3:4]

Participants

9

Reactant 4

HCID 8471Triethylamine2×HCID 824082-Propanesulfonyl chlorideHCID 694231604-[2-(1-Benzyloxycarbonyl-piperidin-3-yloxy)-phenyl]-piperazine-1-carboxylic acid tert-butyl esterHCID 178418361HCID 178418361, compound

Product 1

HCID 694200544-{2-[1-(Propane-2-sulfonyl)-piperidin-3-yloxy]-phenyl}-piperazine-1-carboxylic acid tert-butyl esterYield 80%

Reagents, catalysts & solvents 4

HCID 23938PalladiumCatalystHCID 887MethanolSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent2×

Procedure

4-[2-(1-Benzyloxycarbonyl-piperidin-3-yloxy)-phenyl]-piperazine-1-carboxylic acid tert-butyl ester (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 a silica gel plug with a gradient of 100% ethyl acetate (200 mL) to triethylamine in ethyl acetate (10%). The isolated product (0.382 g, 0.96 mmol) was dissolved in methylene chloride (10 mL) at 0° C., and triethylamine (0.4 mL, 2.9 mmol) was added. Isopropylsulfonyl chloride (0.13 mL, 1.15 mmol) was added dropwise, and the mixture was warmed to r.t. for about 30 minutes, which was then concentrated under reduced pressure and purified using silica gel chromatography (75% ethyl acetate in hexanes) to afford the final compound (0.39 g, 80%).

Workup

  1. customThe catalyst was removed by filtration with ethyl acetate through a bed of celite
  2. customThe compound was isolated
  3. temperaturethe mixture was warmed to r.t. for about 30 minutes
  4. concentrationwhich was then concentrated under reduced pressure
  5. custompurified

Sources & evidence

ORD record
ord-a5851dc30fcb49ae99b9f835e52812e4
Source dataset
uspto-grants-2007_03
Patent number
US07186715B2

Reaction notes

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