Formaldehyde → HCID 54246973, compound

HRID 365922Notes

Reaction equation

HRID 365922 reaction equation
[CH3:1][O:2][CH2:3][CH2:4][O:5][C:6]1[CH:7]=[C:8]([O:12][CH2:13][C@@H:14]2[CH2:18][CH2:17][CH2:16][NH:15]2)[CH:9]=[N:10][CH:11]=1.C=O.[C:21]([O-])(O)=O.[Na+]>C(O)=O>[CH3:1][O:2][CH2:3][CH2:4][O:5][C:6]1[CH:7]=[C:8]([O:12][CH2:13][C@@H:14]2[CH2:18][CH2:17][CH2:16][N:15]2[CH3:21])[CH:9]=[N:10][CH:11]=1

Participants

5

Reactant 3

HCID 712FormaldehydeHCID 516892Sodium BicarbonateHCID 54089941HCID 54089941, compound

Product 1

HCID 54246973HCID 54246973, compoundYield 85%

Reagents, catalysts & solvents 1

HCID 284Formic AcidSolvent

Conditions

Temperature
50 °C

Procedure

To 5-methoxyethoxy-3-(2-(S)-pyrrolidinylmethoxy)pyridine from Example 197f (450 mg, 1.78 mmol) was added formaldehyde (37%, 8 mL) and formic acid (88%, 4 mL), and the mixture was heated at 50° C. for 4 h and then allowed cool to room temperature. The mixture was basified with saturated NaHCO3 and then extracted with Et2O. The organic layer was dried over Na2SO4 and concentrated. The residue was chromatographed (silica gel; hexane/EtOAc, 2:1) to afford the title compound (402 mg, 85%): 1H NMR (CDCl3, 300 MHz) δ 2.00-2.08 (m, 4H), 2.45 (m, 1H), 3.05 (s, 3H), 3.45 (s, 3H), 3.65 (t, 2H, J=6.0 Hz), 3.85 (t, 2H, J=6.0 Hz), 4.15 (m, 1H), 4.30-4.35 (m, 2H), 4.52 (m, 1H), 7.25 (t, 1H, J=3.0 Hz), 8.02 (br s, 2H); MS (CI/NH3) m/z 267 (M+H)+.

Workup

  1. temperatureallowed cool to room temperature
  2. extractionextracted with Et2O
  3. dry with materialThe organic layer was dried over Na2SO4
  4. concentrationconcentrated
  5. customThe residue was chromatographed (silica gel; hexane/EtOAc, 2:1)

Sources & evidence

ORD record
ord-2357298f008e49478457e531a6de1d9e
Source dataset
uspto-grants-2000_10
Patent number
US06127386

Reaction notes

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