Hydrochloric Acid → HCID 54289373, compound

HRID 2305108Notes

Reaction equation

HRID 2305108 reaction equation
[N:1]1[CH:6]=[CH:5][C:4]([CH:7]=[CH:8][C:9]2[CH:10]=[C:11]([O:16][CH2:17][C@@H:18]3[CH2:22][CH2:21][CH2:20][NH:19]3)[CH:12]=[N:13][C:14]=2[Cl:15])=[CH:3][CH:2]=1.[CH2:23]=O.Cl>C(O)=O>[N:1]1[CH:6]=[CH:5][C:4]([CH:7]=[CH:8][C:9]2[CH:10]=[C:11]([O:16][CH2:17][C@@H:18]3[CH2:22][CH2:21][CH2:20][N:19]3[CH3:23])[CH:12]=[N:13][C:14]=2[Cl:15])=[CH:3][CH:2]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 712FormaldehydeHCID 53814515HCID 53814515, compound

Product 1

HCID 54289373HCID 54289373, compoundYield 83%

Reagents, catalysts & solvents 1

HCID 284Formic AcidSolvent

Procedure

To 5-(2-(4-pyridinyl)ethenyl)-6-chloro-3-(2-(S)-pyrrolidinyl-methoxy)pyridine from Example 33 (110 mg, 0.27 mmol) was added formalin (38%, 3.0 mL) and formic acid (88%, 1.5 mL). The mixture was refluxed for five hours then cooled to room temperature. Hydrochloric acid (36%, 0.3 mL) was added, and the mixture was extracted with Et2O (3×8 mL). The aqueous layer was heated under vacuum to dryness. 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 CHCl3/MeOH 10:1 to afford an oil (72 mg, 83%). MS (CI/NH3) m/z 330 (M+H)+. 1H NMR (CDCl3, 300 MHz) δ 1.70-2.10 (m, 4H), 2.38-2.40 (m, 1H), 2.51 (s, 3H), 2.65-2.76 (m, 1H), 3.10-3.19 (m, 1H), 3.96-4.10 (m, 2H), 6.96-7.04 (m, 1H), 7.39-7.44 (m, 2H), 7.53 (s, 1H), 7.52-7.60 (m, 1H), 8.05-8.08 (m, 1H), 8.63-8.67 (m, 1H).

Workup

  1. temperatureThe mixture was refluxed for five hours
  2. extractionthe mixture was extracted with Et2O (3×8 mL)
  3. temperatureThe aqueous layer was heated under vacuum to dryness
  4. additionWater (2 mL) was added
  5. additionsolid sodium bicarbonate was added until the aqueous layer
  6. extractionThe mixture was extracted with EtOAc, which
  7. dry with materialwas dried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe residue was chromatographed on a silica gel column
  11. washeluting with CHCl3/MeOH 10:1

Sources & evidence

ORD record
ord-80e0df44b0354a1f9483ee09276bf704
Source dataset
uspto-grants-2002_08
Patent number
US06437138B1

Reaction notes

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