Ethanol → 8-Oxa-3-azabicyclo[3.2.1]octan-3-yl(4-(4-chlorophenyl)thiazol-2-yl)methanone

HRID 1051879Notes

Reaction equation

HRID 1051879 reaction equation
[CH:1]12[O:8][CH:5]([CH2:6][CH2:7]1)[CH2:4][N:3]([C:9]([C:11]1[S:12][CH:13]=[C:14](Br)[N:15]=1)=[O:10])[CH2:2]2.C(O)C.[Cl:20][C:21]1[CH:26]=[CH:25][C:24](B(O)O)=[CH:23][CH:22]=1.C(=O)([O-])[O-].[K+].[K+]>C1(C)C=CC=CC=1.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>[CH:1]12[O:8][CH:5]([CH2:6][CH2:7]1)[CH2:4][N:3]([C:9]([C:11]1[S:12][CH:13]=[C:14]([C:24]3[CH:25]=[CH:26][C:21]([Cl:20])=[CH:22][CH:23]=3)[N:15]=1)=[O:10])[CH2:2]2

Participants

7

Reactant 4

HCID 702EthanolHCID 11430Potassium CarbonateHCID 742994-Chlorophenylboronic acidHCID 898135378-Oxa-3-azabicyclo[3.2.1]octan-3-yl(4-bromothiazol-2-yl)methanone2×

Product 1

HCID 898134938-Oxa-3-azabicyclo[3.2.1]octan-3-yl(4-(4-chlorophenyl)thiazol-2-yl)methanoneYield 57.8%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 1140TolueneSolvent

Conditions

Temperature
92.5 °C

Procedure

To a solution of 8-oxa-3-azabicyclo[3.2.1]octan-3-yl(4-bromothiazol-2-yl)methanone (Step-1 of compound 67, 1.1 g, 3.63 mmol) in a mixture of toluene:ethanol (5 ml:15 ml) were added (4-chlorophenyl) boronic acid (0.85 g, 5.44 mmol) and potassium carbonate (1.25 g, 9.07 mmol) at 25° C. in a tube, the nitrogen gas was bubbled through reaction mixture for 15 minutes. To the reaction mixture was added tetrakis(triphenylphosphine)palladium(0) (0.41 g, 0.36 mmol) under nitrogen and the tube was sealed. The reaction mixture was heated at 90-95° C. for 18 hr with stirring. The progress of reaction was monitored by TLC; the reaction mixture was cooled to 25° C. and filtered through celite. The residue was washed with mixture of 10% methanol in dichloromethane (2×50 ml). The filtrate was concentrated under reduced pressure to obtain a crude product; which was purified by column chromatography over silica gel (100-200 mesh) using 25% ethyl acetate in hexanes as an eluent to obtain the title compound (0.7 g, 57.8%). MS: m/z 335 (M+1).

Workup

  1. customthe nitrogen gas was bubbled through reaction mixture for 15 minutes
  2. customthe tube was sealed
  3. customThe progress of reaction
  4. temperaturethe reaction mixture was cooled to 25° C.
  5. filtrationfiltered through celite
  6. washThe residue was washed with mixture of 10% methanol in dichloromethane (2×50 ml)
  7. concentrationThe filtrate was concentrated under reduced pressure
  8. customto obtain a crude product
  9. customwhich was purified by column chromatography over silica gel (100-200 mesh)

Sources & evidence

ORD record
ord-bf96efa5a82e46488e4b303ffc2d3d68
Source dataset
uspto-grants-2016_07
Patent number
US09388196B2

Reaction notes

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