3-Bromo-5-((S)-1-methyl-pyrrolidin-2-ylmethoxy)-pyridine → HCID 67585227, compound

HRID 617349Notes

Reaction equation

HRID 617349 reaction equation
Br[C:2]1[CH:3]=[C:4]([O:8][CH2:9][C@@H:10]2[CH2:14][CH2:13][CH2:12][N:11]2[CH3:15])[CH:5]=[N:6][CH:7]=1.[CH2:16]([Mg][Cl:20])[CH2:17][CH3:18]>C1COCC1>[ClH:20].[ClH:20].[CH2:16]([C:2]1[CH:3]=[C:4]([O:8][CH2:9][C@@H:10]2[CH2:14][CH2:13][CH2:12][N:11]2[CH3:15])[CH:5]=[N:6][CH:7]=1)[CH2:17][CH3:18]

Participants

4

Reactant 2

HCID 112887213-Bromo-5-((S)-1-methyl-pyrrolidin-2-ylmethoxy)-pyridineHCID 178455855HCID 178455855, compound

Product 1

HCID 67585227HCID 67585227, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a 1.08 g (4 mmol) sample of 5-bromo-3-((1-methyl-2-(S)-pyrrolidinyl)methoxy)pyridine, prepared as in Example 56a above, dissolved in 30 mL of dry THF and cooled to 0° C. was added 6.0 mL of n-propylmagnesium chloride and 13.0 mg of Ni(dppp)Cl, and the reaction mixture was stirred for 5 hours at room temperature. The reaction was quenched by addition of satd NH4Cl, and the mixture was extracted with chloroform. The solvent was dried over MgSO4 and removed under vacuum, and the residue was purified of a column of silica gel, eluting with 100:1.25:0.025 chloroform:methanol:ammonium hydroxide. The product was converted into the title compound by treatment with HCl in ether according to Example 14c. MS (DCI/NH3) m/e: 235 (M+H)+. 1H NMR (D2O, 300 MHz) δ: 8.28 (s, 1H), 8.23 (s, 1H), 7.78 (m, 1H), 4.58 (dd, J=11.4, 3.7 Hz, 1H), 4.42 (dd, J=11.1, 5.9 Hz, 1H), 3.95 (m, 1H), 3.77 (m, 1H), 3.31-3.25 (m, 1H), 3.05 (s, 3H), 2.74 (t, J=7.3 Hz, 2H), 2.48-2.36 (m, 1H), 2.25-2.06 (m, 3H), 1.68 (m, 2H), 0.91 (t, J=7.4 Hz, 3H). Anal. Calc. for C14H22N2O.1.9 HCl.0.3 ether: C, 56.03; H, 8.22; N, 8.60; Found C, 56.35; H, 8.48; N, 8.73. [α]25D =-3.05° (methanol).

Workup

  1. customThe reaction was quenched by addition of satd NH4Cl
  2. extractionthe mixture was extracted with chloroform
  3. dry with materialThe solvent was dried over MgSO4
  4. customremoved under vacuum
  5. customthe residue was purified of a column of silica gel
  6. washeluting with 100:1.25:0.025 chloroform
  7. custom[α]25D =-3.05° (methanol)

Sources & evidence

ORD record
ord-fc45b1e134864341bdfbfe43ff082ab9
Source dataset
uspto-grants-1999_09
Patent number
US05948793

Reaction notes

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