Formaldehyde → HCID 86755885, compound

HRID 365866Notes

Reaction equation

HRID 365866 reaction equation
[Cl:1][C:2]1[N:7]=[CH:6][C:5]([O:8][CH2:9][C@@H:10]2[CH2:14][CH2:13][CH2:12][NH:11]2)=[CH:4][C:3]=1[C:15]#[C:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH3:22].[CH2:23]=O>C(O)=O>[ClH:1].[ClH:1].[Cl:1][C:2]1[N:7]=[CH:6][C:5]([O:8][CH2:9][C@@H:10]2[CH2:14][CH2:13][CH2:12][N:11]2[CH3:23])=[CH:4][C:3]=1[C:15]#[C:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH3:22]

Participants

4

Reactant 2

HCID 712FormaldehydeHCID 54509584HCID 54509584, compound

Product 1

HCID 86755885HCID 86755885, compoundYield 89%

Reagents, catalysts & solvents 1

HCID 284Formic AcidSolvent

Conditions

Temperature
80 °C

Procedure

To 6-Chloro-5-(1-octynyl)-3-(2-(S)-pyrrolidinylmethoxy)pyridine from Example 140 above (330 mg, 0.78 mmol) was added formalin (37%, 4 mL) and formic acid (2 mL), and the mixture was heated at 80° C. for 10 h. The solvent was concentrated, and solid NaHCO3 was added to the residue. At pH 8 the mixture was extracted with CH2Cl2, which was dried (MgSO4) and concentrated. The residue was chromatographed (silica gel; CH2Cl2/MeOH/NH4OH, 10:1:0.1) to give the free base of the title compound (93 mg, 89% yield). The base was converted to the salt by treatment with HCl in Et2O to give the title compound: mp 223-225° C.; 1H NMR (D2O) δ0.83-0.93 (m, 3H), 1.20-1.30 (m, 4H), 1.34-1.46 (m, 2H), 1.48-1.68 (m, 2H), 1.96-2.20 (m, 3H), 2.28 (m, 1H), 2.34-2.45 (m, 2H), 2.94 (s, 3H), 3.18 (m, 1H), 3.64 (m, 1H), 3.83 (m, 1H), 4.24 (m, 1H), 4.36 (m, 1H), 7.43 (s, 1H), 8.68 (br s, 1H); MS (CI/NH3) m/z 335 (M+H)+. Anal. Calcd for C19H27ClN2O·1.5HCl·0.4 Et2O: C, 59.02; H, 7.81; N, 6.68. Found: C, 59.32; H, 7.54; N, 6.51. [α]25D +8.99 (c 0.14, 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 (MgSO4)
  5. concentrationconcentrated
  6. customThe residue was chromatographed (silica gel; CH2Cl2/MeOH/NH4OH, 10:1:0.1)

Sources & evidence

ORD record
ord-cdf0633980f342afbff80e4eca644ff5
Source dataset
uspto-grants-2000_10
Patent number
US06127386

Reaction notes

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