Cesium carbonate → 2-(Thiazol-2-yl)-2-aza-bicyclo[2.2.2]octan-3-one

HRID 1896300Notes

Reaction equation

HRID 1896300 reaction equation
[CH:1]12[CH2:8][CH2:7][CH:4]([CH2:5][CH2:6]1)[C:3](=[O:9])[NH:2]2.Br[C:11]1[S:12][CH:13]=[CH:14][N:15]=1.C([O-])([O-])=O.[Cs+].[Cs+].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2>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.O1CCOCC1>[S:12]1[CH:13]=[CH:14][N:15]=[C:11]1[N:2]1[C:3](=[O:9])[CH:4]2[CH2:7][CH2:8][CH:1]1[CH2:6][CH2:5]2

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 764302-BromothiazoleHCID 1378872-Azabicyclo(2.2.2)octan-3-oneHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)

Product 1

HCID 673832052-(Thiazol-2-yl)-2-aza-bicyclo[2.2.2]octan-3-oneYield 60%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
125 °C

Procedure

A mixture of 2-azabicyclo[2.2.2]octan-3-one (0.5 g, 4.0 mmol), 2-bromothiazole (0.79 g, 4.81 mmol), Cs2CO3 (2.0 g, 6.0 mmol), xantphos (0.19 g, 0.32 mmol) and 1,4-dioxane (25 ml) was degassed with argon gas for 15 min. Tetrakis(triphenylphosphine)palladium (0) (0.18 g, 0.16 mmol) was added, degassed for another 15 min and stirred at 125° C. for 3 h in a sealed tube. After cooling to room temperature the reaction mixture was filtered and the filtrate was evaporated under reduced pressure to afford the crude compound. Purification by column chromatography over neutral alumina using 10% ethyl acetate in petroleum ether as eluent afford 500 mg (60%) of 2-(thiazol-2-yl)-2-aza-bicyclo[2.2.2]octan-3-one as pale yellow solid.

Workup

  1. customwas degassed with argon gas for 15 min
  2. customdegassed for another 15 min
  3. temperatureAfter cooling to room temperature the reaction mixture
  4. filtrationwas filtered
  5. customthe filtrate was evaporated under reduced pressure
  6. customto afford the crude compound
  7. customPurification by column chromatography over neutral alumina using 10% ethyl acetate in petroleum ether as eluent

Sources & evidence

ORD record
ord-5755ac15d1e1491f8087bb92d6722062
Source dataset
uspto-grants-2013_08
Patent number
US08518948B2

Reaction notes

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