Triethylamine → 3-(2,6-Dichloro-5-nitropyrimidin-4-yl)-8-oxa-3-azabicyclo[3.2.1]octane

HRID 75440

Reaction equation

[Cl:1][C:2]1[N:7]=[C:6]([Cl:8])[C:5]([N+:9]([O-:11])=[O:10])=[C:4](Cl)[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>ClCCl>[Cl:1][C:2]1[N:3]=[C:4]([N:16]2[CH2:15][CH:14]3[O:21][CH:18]([CH2:19][CH2:20]3)[CH2:17]2)[C:5]([N+:9]([O-:11])=[O:10])=[C:6]([Cl:8])[N:7]=1

Participants

Conditions

Temperature: 0 °C

Procedure

2,4,6-Trichloro-5-nitropyrimidine (45, 1.43 g, 6.26 mmoles) was dissolved in dichloromethane and cooled to 0° C. A solution of 8-oxa-3-azabicyclo[3.2.1]octane (2, 0.934 g, 6.26 mmoles) in dichloromethane and triethylamine (0.873 mL, 6.26 mmoles) was slowly added over 1 hour. The solution was allowed to stir at 0° C. for 2 hours, then warmed to room temperature and stirred for an additional 16 hours. The reaction mixture was filtered, the filtrate was concentrated, dissolved in ethyl acetate, washed with 1N hydrochloric acid, saturated sodium bicarbonate, brine, dried, and concentrated to provide 3-(2,6-dichloro-5-nitropyrimidin-4-yl)-8-oxa-3-azabicyclo[3.2.1]octane (46). Yield: 1.53 g (80%). HRMS; [M+H]+ Obs'd=305.0200, [M+H]+ Calc'd=305.0203.

Workup

temperaturewarmed to room temperature
stirringstirred for an additional 16 hours
filtrationThe reaction mixture was filtered
concentrationthe filtrate was concentrated
dissolutiondissolved in ethyl acetate
washwashed with 1N hydrochloric acid, saturated sodium bicarbonate, brine
customdried
concentrationconcentrated

Sources & evidence

ORD record: ord-7de2637b233449baa3af76c79335ccfc
Source dataset: uspto-grants-2014_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08835429B2

Linked notes

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