Formaldehyde → HCID 86750809, compound

HRID 1780346Notes

Reaction equation

HRID 1780346 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([O:9][CH2:10][C@H:11]2[CH2:15][CH2:14][CH2:13][N:12]2[C:16](OC(C)(C)C)=O)[CH:5]=[N:6][C:7]=1[Cl:8].C=O>C(O)=O>[ClH:8].[Br:1][C:2]1[CH:3]=[C:4]([O:9][CH2:10][C@H:11]2[CH2:15][CH2:14][CH2:13][N:12]2[CH3:16])[CH:5]=[N:6][C:7]=1[Cl:8]

Participants

4

Reactant 2

HCID 712FormaldehydeHCID 22872666HCID 22872666, compound

Product 1

HCID 86750809HCID 86750809, compoundYield 119.1%

Reagents, catalysts & solvents 1

HCID 284Formic AcidSolvent

Conditions

Temperature
70 °C

Procedure

To 5-bromo-6-chloro-3-(1-BOC-2-(R)-pyrrolidinylmethoxy)pyridine from step 69a (210 mg, 0.54 mmol) was added formalin (37%, 7 mL) and formic acid (3.5 mL), and the mixture was heated at 70° C. for 2.5 hours. The solvent was concentrated, and solid NaHCO3 was added to the residue. At pH 8 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 100:5-100:10 to afford to give the free base of the title compound (110 mg, 67% yield). MS (DCI/NH3) m/z 305/307 (M+H)+. 1H NMR (CDCl3, 300 MHz) δ1.68 (m, 3H), 2.02 (m, 1H), 2.32 (m, 1H), 2.48 (s, 3H), 2.67 (m, 1H), 3.12 (m, 1H), 3.96 (m, 2H), 7.52 (m, 1H), 8.06 (m, 1H). The base was converted to the salt by treatment with hydrogen chloride in THF to give the title compound. MS (DCI/NH3) m/z 305/207 (M+H)+. 1 H NMR (D2O, 300 MHz) δ: 2.20-2.17 (m, 2H), 2.18-2.31 (m, 1H), 2.32-2.47 (m, 1H), 3.03 (s, 3H), 3.27 (m, 1H), 3.73 (m, 1H), 3.96 (m, 1H), 4.36 (dd, J=6.1, 11.2 Hz, 1H), 4.53 (dd, J=3.1, 11.2 Hz, 1H), 7.91 (d, J=2.7 Hz, 1H), 8.13 (d, J=2.7 Hz, 1H). Anal. Calcd for C11H14N2OBrCl·1.1 HCl: C, 38.22; H, 4.40; N, 8.10. Found: C, 37.95; H, 4.81; N, 7.76. [α]25D =+11.06° (c 0.24, MeOH).

Workup

  1. concentrationThe solvent was concentrated
  2. additionsolid NaHCO3 was added to the residue
  3. extractionAt pH 8 the 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 100:5-100:10
  8. customto afford

Sources & evidence

ORD record
ord-287b3ad901fa4f538da61dec59d3a069
Source dataset
uspto-grants-1997_05
Patent number
US05629325

Reaction notes

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