Formaldehyde → HCID 54465340, compound

HRID 365850Notes

Reaction equation

HRID 365850 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:9]=[C:10]([O:15][CH2:16][C@H:17]3[CH2:21][CH2:20][CH2:19][N:18]3[C:22](OC(C)(C)C)=O)[CH:11]=[N:12][C:13]=2[Cl:14])=[CH:4][CH:3]=1.C=O>C(O)=O>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[CH:9]=[C:10]([O:15][CH2:16][C@H:17]3[CH2:21][CH2:20][CH2:19][N:18]3[CH3:22])[CH:11]=[N:12][C:13]=2[Cl:14])=[CH:6][CH:7]=1

Participants

4

Reactant 2

HCID 712FormaldehydeHCID 22872657HCID 22872657, compound

Product 1

HCID 54465340HCID 54465340, compoundYield 94%

Reagents, catalysts & solvents 1

HCID 284Formic AcidSolvent

Conditions

Temperature
70 °C

Procedure

To 5-(4-chlorophenyl)-6-chloro-3-(1-BOC-2-(R)-pyrrolidinylmethoxy)pyridine from step 76aa (340 mg, 0.8 mmol) was added formalin (37%, 10 mL) and formic acid (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 CH2Cl2, which was dried over MgSO4 and concentrated. The residue was chromatographed on a silica gel column, eluting with CH2Cl2 :MeOH 100:5-100:10 to afford to give the free base of the title compound (255 mg, 94% yield). MS (CI/NH3) m/z 337 (M+H)+. 1H NMR (CDCl3, 300 MHz) δ1.80-2.40 (m, 4H), 2.52 (m, 1H), 2.65 (s, 3H), 2.98 (m, 1H), 3.38 (m, 1H), 4.08 (m, 1H), 4.28 (m, 1H), 7.23 (m, 1H), 7.42 (m, 4H), 8.10 (m, 1H). The base was converted to the salt by treatment with hydrogen chloride in Et2O/THF to give the title compound. mp 176-178° C. MS (CI/NH3) m/z 337 (M+H)+. 1H NMR (D2O, 300 MHz) δ2.06-2.16 (m, 2H), 2.19-2.23 (m, 1H), 2.38-2.41 (m, 1H), 3.03 (s, 3H), 3.24 (m, 1H), 3.74 (m, 1H), 3.91 (m, 1H), 4.36 (dd, J=6.1, 11.2 Hz, 1H), 4.54 (dd, J=3.1, 11.2 Hz, 1H), 7.49-7.57 (m, 5H), 8.14 (d, J=3.0 Hz, 1H). Anal. Calcd for C17H18N2OCl2 ·1.3 HCl: C, 53.08; H, 5.06; N, 7.28. Found: C, 52.93; H, 5.17; N, 7.33. [α]25D=+7.33° (c 2.25, MeOH).

Workup

  1. concentrationThe solvent was concentrated
  2. additionsolid NaHCO3 was added to the residue
  3. extractionAt pH 8 the mixture was extracted with CH2Cl2, which
  4. dry with materialwas dried over MgSO4
  5. concentrationconcentrated
  6. customThe residue was chromatographed on a silica gel column
  7. washeluting with CH2Cl2 :MeOH 100:5-100:10
  8. customto afford

Sources & evidence

ORD record
ord-7e76fdb627b346dfb1fc853fa14ccda5
Source dataset
uspto-grants-2000_10
Patent number
US06127386

Reaction notes

Loading…