Triethylamine → 8-(2-Chloro-6-(chloromethyl)pyrimidin-4-yl)-3-oxa-8-azabicyclo[3.2.1]octane

HRID 75457Notes

Reaction equation

HRID 75457 reaction equation
[Cl:1][C:2]1[N:7]=[C:6](Cl)[CH:5]=[C:4]([CH2:9][Cl:10])[N:3]=1.Cl.[CH:12]12[NH:19][CH:16]([CH2:17][CH2:18]1)[CH2:15][O:14][CH2:13]2.C(N(CC)CC)C>ClCCl>[Cl:1][C:2]1[N:7]=[C:6]([N:19]2[CH:12]3[CH2:18][CH2:17][CH:16]2[CH2:15][O:14][CH2:13]3)[CH:5]=[C:4]([CH2:9][Cl:10])[N:3]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 150017782,4-Dichloro-6-(chloromethyl)pyrimidineHCID 534011293-Oxa-8-azabicyclo(3.2.1)octane hydrochloride

Product 1

HCID 866659078-(2-Chloro-6-(chloromethyl)pyrimidin-4-yl)-3-oxa-8-azabicyclo[3.2.1]octaneYield 69%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A flask was charged with 2,4-dichloro-6-(chloromethyl)pyrimidine (prepared as reported in Bioorg. Med. Chem., 2002, 10, 525), 2.40 g, 12.15 mmol) in dichloromethane (30 mL) to give a yellow solution. 3-Oxa-8-azabicyclo[3.2.1]octane, HCl (33, 1.818 g, 12.15 mmol) and triethylamine (3.56 ml, 25.5 mmol) in dichloromethane (30 mL) were added slowly over 10 minutes, and the resulting solution was allowed to stir at room temperature for 16 hours, then concentrated. The crude product was added to a silica gel column and eluted with 0-40% ethyl acetate in hexanes to provide 8-(2-chloro-6-(chloromethyl)pyrimidin-4-yl)-3-oxa-8-azabicyclo[3.2.1]octane (2.30 g, 69%) as an off-white solid. HRMS; [M+H]+ Obs'd=274.0510, [M+H]+ Calc'd=274.0508

Workup

  1. customto give a yellow solution
  2. concentrationconcentrated
  3. additionThe crude product was added to a silica gel column
  4. washeluted with 0-40% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-10012ad628a540849ce16f926bf6d2d0
Source dataset
uspto-grants-2014_09
Patent number
US08835429B2

Reaction notes

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