Hydrochloric Acid → Tert-butyl 3-[(6-chloro-2-methylpyridin-3-yl)methoxy]azetidine-1-carboxylate

HRID 385983Notes

Reaction equation

[H-].[Na+].[OH:3][CH:4]1[CH2:7][N:6]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:5]1.Br[CH2:16][C:17]1[C:18]([CH3:24])=[N:19][C:20]([Cl:23])=[CH:21][CH:22]=1.Cl>O1CCCC1.O>[Cl:23][C:20]1[N:19]=[C:18]([CH3:24])[C:17]([CH2:16][O:3][CH:4]2[CH2:5][N:6]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:7]2)=[CH:22][CH:21]=1

Participants

Conditions

Temperature: 0 °C

Procedure

Sodium hydride (170 mg of 60%, 4.26 mmol) was suspended in tetrahydrofuran (12 mL) and cooled to 0° C. tert-Butyl 3-hydroxyazetidine-1-carboxylate (246 mg, 1.420 mmol) was added and the slurry was stirred for 30 minutes at 0° C. 3-(Bromomethyl)-6-chloro-2-methylpyridine (Example 421, Step 2) (313 mg, 1.420 mmol) was added and the solution was heated to 50° C. overnight. The reaction mixture was cooled to ambient temperature, diluted with water, acidified with 1 N hydrochloric acid, and extracted with ethyl acetate (2×). The combined organic layers were dried over magnesium sulfate, filtered, concentrated and purified via silica gel chromatography (0-2% methanol in ethyl acetate) to afford the title compound.

Workup

additionwas added
temperaturethe solution was heated to 50° C. overnight
temperatureThe reaction mixture was cooled to ambient temperature
extractionextracted with ethyl acetate (2×)
dry with materialThe combined organic layers were dried over magnesium sulfate
filtrationfiltered
concentrationconcentrated
custompurified via silica gel chromatography (0-2% methanol in ethyl acetate)

Sources & evidence

ORD record: ord-8513b9c64482433a8ddf3968c8cb63e1
Source dataset: uspto-grants-2013_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08367706B2

Reaction notes

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