Sodium hydride → Tert-butyl 3-(5-bromo-2-chloropyrimidin-4-yloxy)azetidine-1-carboxylate

HRID 2194587Notes

Reaction equation

[OH:1][CH:2]1[CH2:5][N:4]([C:6]([O:8][C:9]([CH3:12])([CH3:11])[CH3:10])=[O:7])[CH2:3]1.[H-].[Na+].[H][H].[Br:17][C:18]1[C:19](Cl)=[N:20][C:21]([Cl:24])=[N:22][CH:23]=1>C1COCC1>[Br:17][C:18]1[C:19]([O:1][CH:2]2[CH2:3][N:4]([C:6]([O:8][C:9]([CH3:12])([CH3:11])[CH3:10])=[O:7])[CH2:5]2)=[N:20][C:21]([Cl:24])=[N:22][CH:23]=1

Participants

Conditions

Temperature: 0 °C

Procedure

To a solution of tert-butyl 3-hydroxyazetidine-1-carboxylate (4.1 g, 23.7 mmole) in anhydrous THF (100 mL) at 0° C. was added NaH (60% in mineral oil, 1.33 g, 33.2 mmol). The mixture was stirred at 0° C. for 4 5 min and then room temperature for 2 h until there was no hydrogen bubbles generated. This mixture was added slowly to a solution of 5-bromo-2,4-dichloropyrimidine (10.8 g, 47.4 mmol) in THF (100 mL) at −20° C., and then the reaction mixture was stirred at the same temperature for 2 h and then at room temperature for 3 h. The reaction was quenched with water and extracted with EtOAc. The organic layer was separated, dried (Na2SO4) and concentrated in vacuo. The residue was purified using flash chromatography (silica gel, 5-10% EtOAc in hexanes) to give the title compound (6 g, 70% yield) as a white solid. MS (ESI) m/z: Calc. 363.0 (M+). Found: 309.1 (M++2-tButyl).

Workup

waitroom temperature for 2 h until there was
stirringthe reaction mixture was stirred at the same temperature for 2 h
waitat room temperature for 3 h
customThe reaction was quenched with water
extractionextracted with EtOAc
customThe organic layer was separated
dry with materialdried (Na2SO4)
concentrationconcentrated in vacuo
customThe residue was purified

Sources & evidence

ORD record: ord-6be1dca165044bceb36679ff4677010f
Source dataset: uspto-grants-2012_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08334292B1

Reaction notes

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