Tetrahydrofuran → HCID 54321505, compound

HRID 617359Notes

Reaction equation

HRID 617359 reaction equation
[CH3:1][N:2]1[C@H:6]([CH2:7][O:8][C:9]2[CH:10]=[N:11][CH:12]=[CH:13][CH:14]=2)[CH2:5][CH2:4][C:3]1=O.[CH2:16]1[CH2:20]O[CH2:18][CH2:17]1.C[Li]>CO>[CH2:20]([C@@H:3]1[N:2]([CH3:1])[C@H:6]([CH2:7][O:8][C:9]2[CH:10]=[N:11][CH:12]=[CH:13][CH:14]=2)[CH2:5][CH2:4]1)[CH2:16][CH2:17][CH3:18]

Participants

5

Reactant 3

HCID 8028TetrahydrofuranHCID 54450751(S)-1-Methyl-5-((pyridin-3-yloxy)methyl)pyrrolidin-2-oneHCID 178418348HCID 178418348, compound

Product 1

HCID 54321505HCID 54321505, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
-78 °C

Procedure

A 1.24 g (6.0 mmol) sample of 3-(1-methyl-2-oxo-5-(S)-pyrrolidinylmethoxy)-pyridine, prepared as in Example 22b above, was dissolved in mL of THF and cooled to -78° C. To this solution was added 6.0 mL (12 mmol) of 2 M methyl lithium, and the solution was warmed to room temperature, then stirred for 44 hours. Two mL of methanol were added, and the mixture concentrated under vacuum. Another 10 mL of methanol was added, followed by 65.6 mg of NaBCNH3 and a trace of bromocresol green indicator. HCl (4M) was added slowly until the solution remained a yellow color, then the reaction mixture was stirred for 1 hour. The mixture was then adjusted to basic pH with satd NaHCO3, concentrated, and extracted with ethyl acetate. The extract was dried, concentrated and chromatographed on silica gel to give 86 mg of title compound. MS (DCI/NH3) m/e: 248 (M+H)+. 1H NMR (CDCl3, 300 MHz) δ: 8.33-8.31 (m, 1H), 8.23-8.19 (m, 1H), 7.23-7.19 (m, 2H), 4.11-4.04 (m, 1H), 3.93-3.86 (m, 1H), 2.87-2.77 (m, 1H, 2.46 (s, 3H), 2.40-2.27 (m, 1H), 2.05-1.20 (m, 10H), 0.92 (t, J=6.0 Hz, 3H).

Workup

  1. temperaturethe solution was warmed to room temperature
  2. concentrationthe mixture concentrated under vacuum
  3. additionAnother 10 mL of methanol was added
  4. additionHCl (4M) was added slowly until the solution
  5. stirringthe reaction mixture was stirred for 1 hour
  6. concentrationconcentrated
  7. extractionextracted with ethyl acetate
  8. customThe extract was dried
  9. concentrationconcentrated
  10. customchromatographed on silica gel

Sources & evidence

ORD record
ord-692b59c74f6d46b08da32658452549f4
Source dataset
uspto-grants-1999_09
Patent number
US05948793

Reaction notes

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