Formic Acid → HCID 69832098, compound

HRID 2305111Notes

Reaction equation

HRID 2305111 reaction equation
[ClH:1].Cl.[C:3]1([C:9]2[CH:10]=[C:11]([O:15][CH2:16][C@H:17]3[CH2:21][CH2:20][CH2:19][NH:18]3)[CH:12]=[N:13][CH:14]=2)[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.C=O.[CH:24](O)=O.Cl>CCOCC>[ClH:1].[ClH:1].[C:3]1([C:9]2[CH:10]=[C:11]([O:15][CH2:16][C@H:17]3[CH2:21][CH2:20][CH2:19][N:18]3[CH3:24])[CH:12]=[N:13][CH:14]=2)[CH:4]=[CH:5][CH:6]=[CH:7][CH:8]=1

Participants

6

Reactant 4

HCID 284Formic AcidHCID 313Hydrochloric AcidHCID 712FormaldehydeHCID 69831869HCID 69831869, compound

Product 1

HCID 69832098HCID 69832098, compound

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Procedure

To 5-phenyl-3-(2-(R)-pyrrolidinylmethoxy)pyridine from Example 52 (150 mg, 0.59 mmol) was added formalin (38%, 5.0 mL) and formic acid (88%, 2.5 mL), and the mixture was refluxed for 16 hours. The reaction was quenched by the addition of saturated aqueous NaHCO3. The mixture was extracted with CHCl3, which was dried over MgSO4, filtered and concentrated. The residue was chromatographed on a silica gel column, eluting with CHCl3/MeOH 10:1.5 to afford the base. The salt was prepared by treatment with HCl in Et2O, as described above, to give the title compound. mp. 89-90° C. MS (CI/NH3) m/z 269 (M+H)+. 1H NMR (D2O, 300 MHz) δ: 2.05-2.29 (m, 2H), 2.38-2.47 (m, 1H), 3.07 (s, 3H), 3.23-3.32 (m, 1H), 3.64-3.82 (m, 1H), 3.92-4.00 (m, 1H), 4.44 (dd, J=7.7, 11.0 (1H), 4.61 (dd, J=3.0, 11.2, 1H), 7.51-7.62 (m, 3H), 7.70-7.74 (m, 2H), 7.88 (s, 1H), 8.36 (br s, 1H), 8.56 (br s, 1H). Anal. Calcd for C17H20N2OCl.2 HCl.0.5 H2O: C, 58.29; H, 6.62; N, 8.00. Found: C, 58.16; H, 6.76; N, 8.18. [α]25D=+9.2° (c 0.39, MeOH).

Workup

  1. temperaturethe mixture was refluxed for 16 hours
  2. customThe reaction was quenched by the addition of saturated aqueous NaHCO3
  3. extractionThe mixture was extracted with CHCl3, which
  4. dry with materialwas dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was chromatographed on a silica gel column
  8. washeluting with CHCl3/MeOH 10:1.5
  9. customto afford the base

Sources & evidence

ORD record
ord-7fd4d1b7616e496c80f9c9d61cd55c91
Source dataset
uspto-grants-2002_08
Patent number
US06437138B1

Reaction notes

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