Ethanol → 4-(2-(3-Oxa-8-azabicyclo[3.2.1]octane-8-carbonyl)-4-(4-chlorophenyl)thiazol-5-yl)benzenesulfonamide

HRID 1051877Notes

Reaction equation

HRID 1051877 reaction equation
[CH:1]12[N:8]([C:9]([C:11]3[S:12][C:13](Br)=[C:14]([C:16]4[CH:21]=[CH:20][C:19]([Cl:22])=[CH:18][CH:17]=4)[N:15]=3)=[O:10])[CH:5]([CH2:6][CH2:7]1)[CH2:4][O:3][CH2:2]2.C(O)C.[NH2:27][S:28]([C:31]1[CH:36]=[CH:35][C:34](B(O)O)=[CH:33][CH:32]=1)(=[O:30])=[O:29].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][C:13]([C:34]4[CH:35]=[CH:36][C:31]([S:28]([NH2:27])(=[O:30])=[O:29])=[CH:32][CH:33]=4)=[C:14]([C:16]4[CH:21]=[CH:20][C:19]([Cl:22])=[CH:18][CH:17]=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 223919774-(Aminosulphonyl)benzeneboronic acidHCID 898132963-Oxa-8-azabicyclo[3.2.1]octan-8-yl(5-bromo-4-(4-chlorophenyl)thiazol-2-yl)methanone2×

Product 1

HCID 717371634-(2-(3-Oxa-8-azabicyclo[3.2.1]octane-8-carbonyl)-4-(4-chlorophenyl)thiazol-5-yl)benzenesulfonamideYield 56.3%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 1140TolueneSolvent

Conditions

Temperature
92.5 °C

Procedure

To a solution of 3-oxa-8-azabicyclo[13.2.1]octan-8-yl(5-bromo-4-(4-chlorophenyl) thiazol-2-yl)methanone (Step 3 of compound 68, 0.12 g, 0.29 mmol) in a mixture of toluene:ethanol (2 ml: 6 ml) were added 4-aminosulfonylbenzene boronic acid (0.07 g, 0.35 mmol) and potassium carbonate (0.12 g, 0.87 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) (0.017 g, 0.015 mmol) under nitrogen and 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 ethanol (2×20 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 40% ethyl acetate in hexanes as an eluent to obtain the title compound (0.08 g, 56.3%). MS: m/z 490 (M+1).

Workup

  1. customthe nitrogen gas was bubbled through reaction mixture for 15 minutes
  2. customtube 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 ethanol (2×20 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-f24fe8d1d7d04659a1e099b16ea5ebe0
Source dataset
uspto-grants-2016_07
Patent number
US09388196B2

Reaction notes

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