Sodium Carbonate → HCID 67493806, compound

HRID 1921153Notes

Reaction equation

HRID 1921153 reaction equation
Cl[C:2]1[N:7]=[CH:6][C:5]([C:8]23[CH2:16][N:12]([CH2:13][CH2:14][CH2:15]2)[CH2:11][CH2:10][CH2:9]3)=[CH:4][CH:3]=1.[CH3:17][O:18][C:19]1[CH:20]=[C:21](B(O)O)[CH:22]=[CH:23][C:24]=1[O:25][CH3:26].C(=O)([O-])[O-].[K+].[K+].C(=O)([O-])[O-].[Na+].[Na+]>COCCOC.O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH3:17][O:18][C:19]1[CH:20]=[C:21]([C:2]2[N:7]=[CH:6][C:5]([C:8]34[CH2:16][N:12]([CH2:13][CH2:14][CH2:15]3)[CH2:11][CH2:10][CH2:9]4)=[CH:4][CH:3]=2)[CH:22]=[CH:23][C:24]=1[O:25][CH3:26]

Participants

7

Reactant 4

HCID 10340Sodium CarbonateHCID 11430Potassium CarbonateHCID 27347023,4-Dimethoxyphenylboronic acidHCID 59187101HCID 59187101, compound

Product 1

HCID 67493806HCID 67493806, compound

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 18180031Water 1,2-dimethoxyethaneSolvent

Conditions

Temperature
110 °C

Procedure

0.055 g (0.23 mmol) of 5-(6-chloropyridin-3-yl)-1-azabicyclo[3.3.1]nonane obtained in Example 2, in solution in 12 ml of a 1,2-dimethoxyethane/water 8/4 mixture, is introduced into a 100 ml round-bottomed flask. 0.106 g (0.58 mmol) of 3,4-dimethoxyphenylboronic acid, 0.08 g (0.58 mmol) of potassium carbonate and 0.024 g (0.03 mmol) of dichlorobis(triphenylphosphine)palladium(II) are then successively introduced under an argon atmosphere. The mixture is heated at 110° C. for 2 hours, cooled to ambient temperature and poured into 300 ml of a saturated aqueous sodium carbonate solution. The aqueous phase is extracted twice with 100 ml of chloroform, and the combined organic phases are dried over sodium sulfate and concentrated under reduced pressure. The residue is purified by chromatography on a column of silica gel, elution being carried out with a mixture of chloroform, methanol and aqueous ammonia in the proportions 90/10/1. The compound obtained in the base form (5-[6-(3,4-dimethoxyphenyl)pyridin-3-yl]-1-azabicyclo[3.3.1]nonane) is converted to the hydrochloride by adding two equivalents of hydrochloric acid in solution (5-6 N) in isopropyl alcohol. After triturating from diethyl ether, 0.035 g of the expected product is obtained in the form of a yellow powder.

Workup

  1. temperaturecooled to ambient temperature
  2. extractionThe aqueous phase is extracted twice with 100 ml of chloroform
  3. dry with materialthe combined organic phases are dried over sodium sulfate
  4. concentrationconcentrated under reduced pressure
  5. customThe residue is purified by chromatography on a column of silica gel, elution
  6. additionbeing carried out with a mixture of chloroform, methanol and aqueous ammonia in the proportions 90/10/1

Sources & evidence

ORD record
ord-b424396bd16f4e7e8ba2b9c9d6c1dd6d
Source dataset
uspto-grants-2012_05
Patent number
US08173669B2

Reaction notes

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