Sodium Carbonate → HCID 15480238, compound

HRID 2305087Notes

Reaction equation

HRID 2305087 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+].[CH3:22][O:23][C:24]1[CH:29]=[CH:28][C:27](B(O)O)=[CH:26][CH:25]=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>[CH3:22][O:23][C:24]1[CH:29]=[CH:28][C:27]([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)=[CH:26][CH:25]=1

Participants

8

Reactant 4

HCID 10340Sodium CarbonateHCID 201262(4-Methoxyphenyl)boronic acidHCID 516892Sodium BicarbonateHCID 112887213-Bromo-5-((S)-1-methyl-pyrrolidin-2-ylmethoxy)-pyridine

Product 1

HCID 15480238HCID 15480238, compoundYield 58.3%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 241BenzeneSolventHCID 962WaterSolvent

Procedure

To s solution of 5-bromo-3-(1-methyl-2-(S)-pyrrolidinylmethoxy)-pyridine (272 mg, 1.00 mmol) in benzene (2.0 mL) were added sodium carbonate (2.0 M, 1.0 mL), tetrakis(triphenylphosphine)palladium(0) (35 mg, 0.03 mmol) and 4-methoxyphenylboronic acid (228 mg, 1.30 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 (174 mg, 58%). MS (CI/NH3) m/z 299 (M+H)+. 1H NMR (CDCl3, 300 MHz) δ 1.71-1.92 (m, 3H), 1.99-2.10 (m, 1H), 2.51 (s, 3H), 2.65-2.74 (m, 1H), 3.09-3.17 (m, 1H), 3.87 (s, 3H), 3.96-4.11 (m, 2H), 7.00 (d, J=8.8 Hz, 1H), 7.36 (t, J=3.0 Hz, J=2.1 Hz, 1H), 7.52 (d, J=8.8 Hz, 1H), 8.27 (d, J=3.0 Hz, 1H), 8.42 (d, J=2.1 Hz, 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-9335de46924a4509b80bec676f698c13
Source dataset
uspto-grants-2002_08
Patent number
US06437138B1

Reaction notes

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