Formaldehyde → HCID 86750807, compound

HRID 1780342Notes

Reaction equation

HRID 1780342 reaction equation
[C:1]1([C:7]2[CH:8]=[C:9]([O:14][CH2:15][C@H:16]3[CH2:20][CH2:19][CH2:18][N:17]3[C:21](OC(C)(C)C)=O)[CH:10]=[N:11][C:12]=2[Cl:13])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C=O>C(O)=O>[ClH:13].[C:1]1([C:7]2[CH:8]=[C:9]([O:14][CH2:15][C@H:16]3[CH2:20][CH2:19][CH2:18][N:17]3[CH3:21])[CH:10]=[N:11][C:12]=2[Cl:13])[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1

Participants

4

Reactant 2

HCID 712FormaldehydeHCID 22872686HCID 22872686, compound

Product 1

HCID 86750807HCID 86750807, compoundYield 175%

Reagents, catalysts & solvents 1

HCID 284Formic AcidSolvent

Conditions

Temperature
70 °C

Procedure

To the 5-phenyl-6-chloro-3-(1-BOC-2-(R)-pyrrolidinylmethoxy)pyridine compound from step 69b (262 mg) was added formalin (37%, 0.5 mL) and formic acid (0.25 mL), and the mixture was heated at 70° C. for 3 hours. The solvent was removed, and to the residue was added solid NaHCO3. When pH 7-8 was achieved, the mixture was extracted with methylene chloride, which was dried over MgSO4 and concentrated. The residue was chromatographed on a silica gel column, eluting with methylene chloride:methanol:NH4OH 100:10:0.04 to afford to give the free base of the title compound (200 mg). MS (DCI/NH3) m/z 303 (M+H)+. 1H NMR (CDCl3, 300 MHz) δ1.98 (m, 2H), 2.10 (m, 1H), 2.22 (m, 1H), 2.71 (m, 1H), 2.78 (s, 3H), 3.27 (m, 1H), 3.60 (m, 1H), 4.18 (m, 1H), 4.47 (m, 1H), 7.46 (m, 5H), 8.10 (m, 1H), 8.30 (br s, 1H). The base was converted to the salt by treatment with HCl in THF to give the title compound. MS (DCI/NH3) m/z 303 (M+H)+. 1H NMR (D2O, 300 MHz) δ: 2.05-2.17 (m, 2H), 2.19-2.27 (m, 1H), 2.35-2.45 (m, 1H), 3.04 (s, 3H), 3.30 (m, 1H), 3.74 (m, 1H), 3.94 (m, 1H), 4.37 (dd, J=6.1, 11.2 Hz, 1H), 4.54 (dd, J=3.3, 11.2 Hz, 1H), 7.56 (m, 6H), 8.15 (d, J=3.0 Hz, 1H). Anal. Calcd for C17H19N2OCl·1.1 HCl: C, 59.55; H, 5.91; N, 8.17. Found: C, 59.74; H, 6.04; N, 8.14. [α]25D =+7.17° (c 1.11, MeOH).

Workup

  1. customThe solvent was removed
  2. additionto the residue was added solid NaHCO3
  3. extractionthe mixture was extracted with methylene chloride, which
  4. dry with materialwas dried over MgSO4
  5. concentrationconcentrated
  6. customThe residue was chromatographed on a silica gel column
  7. washeluting with methylene chloride:methanol:NH4OH 100:10:0.04
  8. customto afford

Sources & evidence

ORD record
ord-97a02b8655024d6ebbc9579e6f07bee7
Source dataset
uspto-grants-1997_05
Patent number
US05629325

Reaction notes

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