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

HRID 1051875Notes

Reaction equation

HRID 1051875 reaction equation
[CH:1]12[N:8]([C:9]([C:11]3[S:12][CH:13]=[C:14](Br)[N:15]=3)=[O:10])[CH:5]([CH2:6][CH2:7]1)[CH2:4][O:3][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[N:8]([C:9]([C:11]3[S:12][CH:13]=[C:14]([C:24]4[CH:25]=[CH:26][C:21]([Cl:20])=[CH:22][CH:23]=4)[N:15]=3)=[O:10])[CH:5]([CH2:6][CH2:7]1)[CH2:4][O:3][CH2:2]2

Participants

7

Reactant 4

HCID 702EthanolHCID 11430Potassium CarbonateHCID 742994-Chlorophenylboronic acidHCID 898133463-Oxa-8-azabicyclo[3.2.1]octan-8-yl(4-bromothiazol-2-yl)methanone2×

Product 1

HCID 898132053-Oxa-8-azabicyclo[3.2.1]octan-8-yl(4-(4-chlorophenyl)thiazol-2-yl)methanoneYield 51.9%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 1140TolueneSolvent

Conditions

Temperature
92.5 °C

Procedure

To a solution of 3-oxa-8-azabicyclo[3.2.1]octan-8-yl(4-bromothiazol-2-yl)methanone (Step-1 of compound 68, 0.35 g, 1.15 mmol) in a mixture of toluene:ethanol (2.5 ml: 7.5 ml) were added (4-chlorophenyl) boronic acid (0.2 g, 1.27 mmol) and potassium carbonate (0.34 g, 2.42 mmol) at 25° C. in a tube, nitrogen gas was bubbled through reaction mixture for 15 minutes. To the reaction mixture was added tetrakis(triphenylphosphine)palladium(0) (0.07 g, 0.06 mmol) under nitrogen, tube was sealed and 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 ethanol (2×20 ml). The filtrate was concentrated under reduced pressure to obtain a crude product. This crude product was purified by column chromatography over silica gel (100-200 mesh) using 35% ethyl acetate in hexanes as an eluent to obtain the title compound (0.2 g, 51.7%). MS: m/z 335 (M+1).

Workup

  1. customnitrogen gas was bubbled through reaction mixture for 15 minutes
  2. customtube was sealed
  3. customreaction mixture
  4. customThe progress of reaction
  5. temperatureThe reaction mixture was cooled to 25° C.
  6. filtrationfiltered through celite
  7. washThe residue was washed with ethanol (2×20 ml)
  8. concentrationThe filtrate was concentrated under reduced pressure
  9. customto obtain a crude product
  10. customThis crude product was purified by column chromatography over silica gel (100-200 mesh)

Sources & evidence

ORD record
ord-c587f10ec0e94b47a5bc394df6390bff
Source dataset
uspto-grants-2016_07
Patent number
US09388196B2

Reaction notes

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