Hydrochloric Acid → 4-{2-[(6-Chloro-2-methylpyridin-3-yl)methoxy]ethyl}morpholin-3-one

HRID 385981Notes

Reaction equation

[H-].[Na+].[OH:3][CH2:4][CH2:5][N:6]1[CH2:11][CH2:10][O:9][CH2:8][C:7]1=[O:12].Br[CH2:14][C:15]1[C:16]([CH3:22])=[N:17][C:18]([Cl:21])=[CH:19][CH:20]=1.Cl>C1COCC1.O>[Cl:21][C:18]1[N:17]=[C:16]([CH3:22])[C:15]([CH2:14][O:3][CH2:4][CH2:5][N:6]2[CH2:11][CH2:10][O:9][CH2:8][C:7]2=[O:12])=[CH:20][CH:19]=1

Participants

Conditions

Temperature: 0 °C

Procedure

Sodium hydride (190 mg of a 60%, 4.76 mmol) was suspended in THF (12.2 mL) and cooled to 0° C. 4-(2-Hydroxyethyl)morpholin-3-one (230 mg, 1.59 mmol) was added and the slurry was stirred for thirty minutes at 0° C. 3-(Bromomethyl)-6-chloro-2-methylpyridine (Example 421 Step 2) (350 mg, 1.59 mmol) was added and the solution was heated to 50° C. overnight. The reaction mixture was then cooled to ambient temperature, diluted with water, acidified using 1 N aqueous hydrochloric acid, and extracted with ethyl acetate (2×). The combined organic layers were dried over magnesium sulfate, filtered, concentrated, and purified by silica gel chromatography (0-2% methanol in ethyl acetate) to afford the title compound.

Workup

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

Sources & evidence

ORD record: ord-9cc50da4fccd40e0a10e57c7a83005c9
Source dataset: uspto-grants-2013_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08367706B2

Reaction notes

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