Sodium Hydroxide → HCID 58485547, compound

HRID 2179667Notes

Reaction equation

HRID 2179667 reaction equation
CC1(C)C(C)(C)OB([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=2[NH2:15])O1.[OH-].[Na+].[N:19]12[CH2:26][CH2:25][CH:22]([CH2:23][CH2:24]1)[C@@H:21]([NH:27][C:28]([C:30]1[O:31][C:32]3[C:38](Br)=[CH:37][CH:36]=[CH:35][C:33]=3[CH:34]=1)=[O:29])[CH2:20]2>CN(C=O)C.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[NH2:15][C:10]1[CH:11]=[CH:12][CH:13]=[CH:14][C:9]=1[C:38]1[C:32]2[O:31][C:30]([C:28]([NH:27][C@@H:21]3[CH:22]4[CH2:23][CH2:24][N:19]([CH2:26][CH2:25]4)[CH2:20]3)=[O:29])=[CH:34][C:33]=2[CH:35]=[CH:36][CH:37]=1

Participants

6

Reactant 3

HCID 14798Sodium HydroxideHCID 27346522-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)anilineHCID 59341359HCID 59341359, compound

Product 1

HCID 58485547HCID 58485547, compound

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
95 °C

Procedure

752 mg (3.44 mmol) of 2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenylamine and 11.45 ml of 1N sodium hydroxide solution are added to a mixture of 1.0 g (2.86 mmol) of N-[(3R)-1-azabicyclo[2.2.2]oct-3-yl]-7-bromo-1-benzofuran-2-carboxamide (Example 30A) and 234 mg (0.29 mmol) of PdCl2(dppf) in 15 ml of DMF. The reaction mixture is heated at 95° C. overnight and then filtered through kieselguhr. The solvent is then removed under reduced pressure, and the residue is taken up in 100 ml of ethyl acetate and 100 ml of 1N sodium hydroxide solution. The organic phase is washed twice with 1N sodium hydroxide solution and once with saturated sodium chloride solution. The combined organic phases are dried over magnesium sulphate, and the solvent is removed in a rotary evaporator under reduced pressure. The crude product is taken up in methanol and shaken together with acidic ion exchanger (Dowex® WX2-200) for about 30 min. The loaded ion exchanger is washed three times with 30 ml of methanol each time and then with DMF. It is washed successively with methanol, dichloromethane, methanol, water, methanol, dichloromethane, methanol, THF and finally once again with methanol. The product is eluted with methanol/triethylamine 95:5. The solvent is removed in a rotary evaporator under reduced pressure. Drying under high vacuum results in 601 mg (48% of theory) of the title compound in sufficient purity for further reactions.

Workup

  1. filtrationfiltered through kieselguhr
  2. customThe solvent is then removed under reduced pressure
  3. washThe organic phase is washed twice with 1N sodium hydroxide solution and once with saturated sodium chloride solution
  4. dry with materialThe combined organic phases are dried over magnesium sulphate
  5. customthe solvent is removed in a rotary evaporator under reduced pressure
  6. washThe loaded ion exchanger is washed three times with 30 ml of methanol each time
  7. washIt is washed successively with methanol, dichloromethane, methanol, water, methanol, dichloromethane, methanol, THF and finally once again with methanol
  8. washThe product is eluted with methanol/triethylamine 95:5
  9. customThe solvent is removed in a rotary evaporator under reduced pressure
  10. customDrying under high vacuum

Sources & evidence

ORD record
ord-3d6995ae42c44b23a440c1e00ecd164b
Source dataset
uspto-grants-2015_06
Patent number
US09067931B2

Reaction notes

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