Formic Acid → HCID 69832098, compound

HRID 365829Notes

Reaction equation

HRID 365829 reaction equation
[C:1]1([C:7]2[CH:8]=[C:9]([O:13][CH2:14][C@H:15]3[CH2:19][CH2:18][CH2:17][NH:16]3)[CH:10]=[N:11][CH:12]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C=O.[CH:22](O)=O.[ClH:25]>CCOCC>[ClH:25].[ClH:25].[C:1]1([C:7]2[CH:8]=[C:9]([O:13][CH2:14][C@H:15]3[CH2:19][CH2:18][CH2:17][N:16]3[CH3:22])[CH:10]=[N:11][CH:12]=2)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1

Participants

6

Reactant 4

HCID 284Formic AcidHCID 313Hydrochloric AcidHCID 712FormaldehydeHCID 53974852HCID 53974852, 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) δ2.05-2.29 (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-f2b9339683b6406f827fd8eea8da6d10
Source dataset
uspto-grants-2000_10
Patent number
US06127386

Reaction notes

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