Sodium Carbonate → 3-((S)-1-Methyl-pyrrolidin-2-ylmethoxy)-5-naphthalen-1-yl-pyridine

HRID 1780296Notes

Reaction equation

HRID 1780296 reaction equation
Br[C:2]1[CH:3]=[C:4]([O:8][CH2:9][C@@H:10]2[CH2:14][CH2:13][CH2:12][N:11]2[CH3:15])[CH:5]=[N:6][CH:7]=1.C(=O)([O-])[O-].[Na+].[Na+].[C:22]1(B(O)O)[C:31]2[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=2)[CH:25]=[CH:24][CH:23]=1.C(=O)(O)[O-].[Na+]>C1C=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.O>[C:30]1([C:2]2[CH:3]=[C:4]([O:8][CH2:9][C@@H:10]3[CH2:14][CH2:13][CH2:12][N:11]3[CH3:15])[CH:5]=[N:6][CH:7]=2)[C:31]2[C:26](=[CH:25][CH:24]=[CH:23][CH:22]=2)[CH:27]=[CH:28][CH:29]=1

Participants

8

Reactant 4

HCID 10340Sodium CarbonateHCID 2545321-Naphthaleneboronic acidHCID 516892Sodium BicarbonateHCID 112887213-Bromo-5-((S)-1-methyl-pyrrolidin-2-ylmethoxy)-pyridine

Product 1

HCID 104260413-((S)-1-Methyl-pyrrolidin-2-ylmethoxy)-5-naphthalen-1-yl-pyridineYield 62%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 241BenzeneSolventHCID 962WaterSolvent

Procedure

To a solution of 5-bromo-3-(1-methyl-2-(S)-pyrrolidinylmethoxy)-pyridine (272 mg, 1.00 mmol) in benzene (2.0 mL) were added aqueous sodium carbonate (2.0M, 1.0 mL), tetrakis(triphenylphosphine)palladium(0) (35 mg, 0.03 mmol) and 1-naphthaleneboronic acid (189 mg, 1.10 mmol). The reaction mixture was refluxed overnight, then cooled to room temperature. Water (2 mL) was added, and solid sodium bicarbonate was added until the aqueous layer was saturated. The mixture was extracted with EtOAc, which was dried over MgSO4, filtered and concentrated. The residue was chromatographed on a silica gel column, eluting with NH4OH/MeOH/EtOAc 0:1:9 and 1:10:90 to afford a light yellowish oil (196 mg, 62%). MS (CI/NH3) m/z 319 (M+H)+. 1H NMR (CDCl3, 300 MHz) δ1.71-1.92 (m, 3H), 2.00-2.10 (m, 1H), 2.27-2.38 (m, 1H), 2.51 (s, 3H), 2.66-2.75 (m, 1H), 3.09-3.17 (m, 1H), 3.98-4.14 (m, 2H), 7.34-7.57 (m, 5H), 7.72-7.96 (m, 3H), 8.36-8.43 (m, 1H).

Workup

  1. temperatureThe reaction mixture was refluxed overnight
  2. extractionThe mixture was extracted with EtOAc, which
  3. dry with materialwas dried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was chromatographed on a silica gel column
  7. washeluting with NH4OH/MeOH/EtOAc 0:1:9 and 1:10:90

Sources & evidence

ORD record
ord-7d1354cd2d6d4a94be5fb82b4a87b3de
Source dataset
uspto-grants-1997_05
Patent number
US05629325

Reaction notes

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