Tetrahydrofuran → Ammonium Hydroxide

HRID 617347Notes

Reaction equation

HRID 617347 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[Mg]Br.[CH2:19]1COC[CH2:20]1>>[OH-:8].[NH4+:6].[CH2:19]([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)[CH3:20]

Participants

5

Reactant 3

HCID 8028TetrahydrofuranHCID 112887213-Bromo-5-((S)-1-methyl-pyrrolidin-2-ylmethoxy)-pyridineHCID 178418573HCID 178418573, compound

Product 2

HCID 14923Ammonium HydroxideHCID 44318995HCID 44318995, compound

Conditions

Temperature
0 °C

Procedure

A 542 mg (2 mmol) sample of 5-bromo-3-(1-methyl-2-(S)-pyrrolidinylmethoxy)-pyridine, from Example 28 above, was dissolved in 10 mL of THF, 6.6 mg of Ni(dppp)Cl was added, and the mixture was cooled to 0° C. To this solution was added 0.6 mL of methylmagnesium bromide, then the mixture was stirred at room temperature for 5 hours. The reaction was quenched by addition of NH4Cl solution, and the mixture was extracted with CHCl3. The organic extract was dried and concentrated. The residue was purified by chromatography on silica gel, eluting with 100:1.25:0.025 chloroform: methanol:ammonium hydroxide, to give 40 mg of the title compound. MS (DCI/NH3) m/e: 221 (M+H)+. 1H NMR (CDCl3,300 MHz) δ: 8.16 (d, J=2.4 Hz, 1H), 8.08 (d, J=1.2 Hz, 1H), 7.06 (t, J=2.4 Hz, 1H), 4.02 (dd, J=9.3, 5.4 Hz, 1H), 3.92 (dd, J=9.0, 6.0 Hz, 1H), 3.12 (m, 1H), 2.70-2.59 (m, 3H), 2.49 (s, 3H), 2.32 (m, 1H), 2.04 (m, 1H), 1.93-1.68 (m, 3H), 1.25 (t, J=7.80, 3H).

Workup

  1. customThe reaction was quenched by addition of NH4Cl solution
  2. extractionthe mixture was extracted with CHCl3
  3. extractionThe organic extract
  4. customwas dried
  5. concentrationconcentrated
  6. customThe residue was purified by chromatography on silica gel
  7. washeluting with 100:1.25:0.025 chloroform

Sources & evidence

ORD record
ord-5c66b9d4d1c8442ea5800ac982146a4f
Source dataset
uspto-grants-1999_09
Patent number
US05948793

Reaction notes

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