Triethylamine → 3-(2,6-Dichloro-pyrimidin-4-yl)-8-oxa-3-aza-bicyclo[3.2.1]octane

HRID 75410

Reaction equation

HRID 75410 reaction equation
[Cl:1][C:2]1[N:7]=[C:6]([Cl:8])[CH:5]=[C:4]([Cl:9])[N:3]=1.Cl.[CH:11]12[O:18][CH:15]([CH2:16][CH2:17]1)[CH2:14][NH:13][CH2:12]2.CCN(CC)CC>CCO>[Cl:1][C:2]1[N:3]=[C:4]([N:13]2[CH2:12][CH:11]3[O:18][CH:15]([CH2:16][CH2:17]3)[CH2:14]2)[CH:5]=[C:6]([Cl:8])[N:7]=1.[Cl:9][C:4]1[CH:5]=[C:6]([Cl:8])[N:7]=[C:2]([N:13]2[CH2:12][CH:11]3[O:18][CH:15]([CH2:16][CH2:17]3)[CH2:14]2)[N:3]=1

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 773782,4,6-TrichloropyrimidineHCID 219835368-Oxa-3-aza-bicyclo(3.2.1)octane hydrochloride

Product 2

HCID 866658793-(2,6-Dichloro-pyrimidin-4-yl)-8-oxa-3-aza-bicyclo[3.2.1]octaneYield 83%HCID 866658803-(4,6-Dichloro-pyrimidin-2-yl)-8-oxa-3-aza-bicyclo[3.2.1]octaneYield 11%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

2,4,6-Trichloropyrimidine (8, 6.325 mL, 55 mmol) was dissolved in 220 mL EtOH at 0° C. 8-Oxa-3-aza-bicyclo[3.2.1]octane hydrochloride (2, 8.23 g, 55 mmol) was added followed by the addition of NEt3 (23.1 mL, 165 mmol). The mixture was allowed to warm to room temperature and stirred for 1 hour at ambient temperature. The mixture was concentrated, dissolved in EtOAc and washed with saturated NaHCO3. The aqueous phase was extracted with EtOAc the combined organic phases were dried (MgSO4), filtered, and concentrated. The mixture was purified by silica gel chromatography (10-80% EtOAc in hexanes) to give 11.807 g (45 mmol, 83%) of 3-(2,6-dichloro-pyrimidin-4-yl)-8-oxa-3-aza-bicyclo[3.2.1]octane (9) along with 1.631 g (6.2 mmol, 11%) of 3-(4,6-dichloro-pyrimidin-2-yl)-8-oxa-3-aza-bicyclo[3.2.1]octane (10).

Workup

  1. concentrationThe mixture was concentrated
  2. dissolutiondissolved in EtOAc
  3. washwashed with saturated NaHCO3
  4. extractionThe aqueous phase was extracted with EtOAc the combined organic phases
  5. dry with materialwere dried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe mixture was purified by silica gel chromatography (10-80% EtOAc in hexanes)

Sources & evidence

ORD record
ord-7ccd338c5fbb421d822032d9cc5cadba
Source dataset
uspto-grants-2014_09
Patent number
US08835429B2

Linked notes

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