Hydrochloric Acid → HCID 54289373, compound

HRID 365827Notes

Reaction equation

HRID 365827 reaction equation
Cl.Cl.[N:3]1[CH:8]=[CH:7][C:6]([CH:9]=[CH:10][C:11]2[CH:12]=[C:13]([O:18][CH2:19][C@@H:20]3[CH2:24][CH2:23][CH2:22][NH:21]3)[CH:14]=[N:15][C:16]=2[Cl:17])=[CH:5][CH:4]=1.[CH2:25]=O.Cl>C(O)=O>[N:3]1[CH:8]=[CH:7][C:6]([CH:9]=[CH:10][C:11]2[CH:12]=[C:13]([O:18][CH2:19][C@@H:20]3[CH2:24][CH2:23][CH2:22][N:21]3[CH3:25])[CH:14]=[N:15][C:16]=2[Cl:17])=[CH:5][CH:4]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 712FormaldehydeHCID 86758466HCID 86758466, 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) δ1.70-2.10 (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-986b6e6b55064f9f861b463f4fcd2dc6
Source dataset
uspto-grants-2000_10
Patent number
US06127386

Reaction notes

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