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

HRID 75450Notes

Reaction equation

HRID 75450 reaction equation
[Cl:1][C:2]1[N:7]=[C:6](Cl)[CH:5]=[C:4]([C:9]([F:12])([F:11])[F:10])[N:3]=1.Cl.[CH:14]12[O:21][CH:18]([CH2:19][CH2:20]1)[CH2:17][NH:16][CH2:15]2.C(N(CC)CC)C>C(OCC)C.C(O)C>[Cl:1][C:2]1[N:7]=[C:6]([N:16]2[CH2:15][CH:14]3[O:21][CH:18]([CH2:19][CH2:20]3)[CH2:17]2)[CH:5]=[C:4]([C:9]([F:12])([F:11])[F:10])[N:3]=1

Participants

6

Reactant 3

HCID 8471Triethylamine2×HCID 3342032,4-Dichloro-6-(trifluoromethyl)pyrimidineHCID 219835368-Oxa-3-aza-bicyclo(3.2.1)octane hydrochloride2×

Product 1

HCID 866659013-(2-Chloro-6-trifluoromethyl-pyrimidin-4-yl)-8-oxa-3-aza-bicyclo[3.2.1]octaneYield 120.2%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 3283Diethyl EtherSolvent

Procedure

A solution of crude 2,4-dichloro-6-(trifluoromethyl)pyrimidine (62, 6.7 mmol) in diethyl ether (10 mL) was diluted with ethanol (25 mL) and cooled in an ice-water bath. 8-Oxa-3-azabicyclo[3.2.1]octane hydrochloride (2, 3.4 mmol) was added, followed by triethylamine (2 mL). Two additional portions of 8-oxa-3-azabicyclo[3.2.1]octane hydrochloride (2, 100 mg each) were added, the mixture was slowly warmed to room temperature and stirred overnight. Additional triethylamine (4 mL) was added to the mixture, which was then concentrated to dryness under reduced pressure. The residue was purified via flash silica gel chromatography (40% ethyl acetate/hexanes) to provide the title compound as a light colored solid (1.2 g, 61%). MS (ES+): 294.2 (M+H)+.

Workup

  1. temperaturecooled in an ice-water bath
  2. concentrationwas then concentrated to dryness under reduced pressure
  3. customThe residue was purified via flash silica gel chromatography (40% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-388ffe1582cc46c48dd18fce67d6cdc3
Source dataset
uspto-grants-2014_09
Patent number
US08835429B2

Reaction notes

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