Cesium carbonate → HCID 60042063, compound

HRID 2362857Notes

Reaction equation

HRID 2362857 reaction equation
[N:1]12[CH2:8][CH2:7][CH:4]([CH2:5][CH2:6]1)[C@H:3]([NH:9][C:10]([C:12]1[C:16]3[CH:17]=[CH:18][C:19](Br)=[CH:20][C:15]=3S[N:13]=1)=[O:11])[CH2:2]2.C[C:23]1(C)[C:36]2[CH:35]=[CH:34][CH:33]=[C:32](P(C3C=CC=CC=3)C3C=CC=CC=3)[C:31]=2OC2C1=CC=CC=2P(C1C=CC=CC=1)C1C=CC=CC=1.[C:64](=[O:67])([O-])[O-].[Cs+].[Cs+].[C:70](=[NH:83])([C:77]1[CH:82]=[CH:81]C=CC=1)C1C=CC=CC=1>C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[N:1]12[CH2:8][CH2:7][CH:4]([CH2:5][CH2:6]1)[C@H:3]([NH:9][C:10]([C:12]1[C:16]3[C:15](=[CH:20][CH:19]=[C:18]([N:1]4[CH2:2][CH2:3][CH:64]([O:67][CH2:23][C:36]5[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=5)[CH2:6]4)[CH:17]=3)[N:83]([CH2:70][CH:77]3[CH2:82][CH2:81]3)[N:13]=1)=[O:11])[CH2:2]2

Participants

6

Reactant 4

HCID 10796Cesium carbonateHCID 136809Benzophenone imineHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 10044409HCID 10044409, compound

Product 1

HCID 60042063HCID 60042063, compoundYield 79%

Reagents, catalysts & solvents 1

HCID 167845palladium(II) acetateCatalyst

Procedure

The mixture of N-[(3S)-1-azabicyclo[2.2.2]oct-3-yl]-6-bromo-1,2-benzisothiazole-3-carboxamide (6.30 mmol), palladium acetate (1.00 mmol), and 9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene (Xantphos) (0.700 mmol) was evacuated and back-fill with Ar gas. The solids were diluted with tetrahydrofuran (150 mL) and treated with cesium carbonate (7.00 mmol) and benzophenone imine (6.80 mmol). The reaction mixture was heated at reflux for 16 h. The reaction mixture was concentrated and redissolved in a mixture of tetrahydrofuran (90 mL) and 3 N hydrochloric acid (30 mL). The reaction mixture was maintained for 2 h and was concentrated. The residue was purified by chromatography using a mixture of 70/30/1 ethyl acetate/methanol/ammonium hydroxide, thus providing the aniline in 79% yield. The aniline was used directly in subsequent reactions.

Workup

  1. customwas evacuated and back-fill with Ar gas
  2. additionThe solids were diluted with tetrahydrofuran (150 mL)
  3. temperatureThe reaction mixture was heated
  4. temperatureat reflux for 16 h
  5. concentrationThe reaction mixture was concentrated
  6. dissolutionredissolved in a mixture of tetrahydrofuran (90 mL) and 3 N hydrochloric acid (30 mL)
  7. temperatureThe reaction mixture was maintained for 2 h
  8. concentrationwas concentrated
  9. customThe residue was purified by chromatography
  10. additiona mixture of 70/30/1 ethyl acetate/methanol/ammonium hydroxide

Sources & evidence

ORD record
ord-a2a3e72e1106410eb795d7e7e3fceae1
Source dataset
uspto-grants-2014_04
Patent number
US08691841B2

Reaction notes

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