3-Fluorobenzyl bromide → 5-[(3-Fluorobenzyl)sulfanyl]-2,3-bis(methoxymethoxy)pyridine

HRID 709057Notes

Reaction equation

[CH3:1][O:2][CH2:3][O:4][C:5]1[CH:6]=[C:7]([S:15][CH2:16][CH2:17][C:18](OC)=O)[CH:8]=[N:9][C:10]=1[O:11][CH2:12][O:13][CH3:14].[K].[O-]CCCC.BrC[C:30]1C=C[CH:33]=[C:32]([F:36])[CH:31]=1>C1COCC1>[F:36][C:32]1[CH:33]=[C:17]([CH:18]=[CH:30][CH:31]=1)[CH2:16][S:15][C:7]1[CH:6]=[C:5]([O:4][CH2:3][O:2][CH3:1])[C:10]([O:11][CH2:12][O:13][CH3:14])=[N:9][CH:8]=1

Participants

Conditions

Temperature: -45 °C

Procedure

To a solution of methyl 3-{[5,6-bis(methoxymethoxy)pyridin-3-yl]sulfanyl}propanoate (Intermediate 42; 1 g, 3.15 mmol) in THF (17 ml) at −45° C. was added potassium ten-butoxide (0.389 g, 3.47 mmol). After stirring at −45° C. temperature for 1 hour, 1-(bromomethyl)-3-fluorobenzene (0.715 g, 3.78 mmol) was added and the reaction mixture stirred for 3 hours. Upon warming to room temperature the reaction mixture was partitioned between dichloromethane and water. The aqueous phase was re-extracted and the combined organic extracts were washed with brine, dried and concentrated in vacuo. The crude product was purified by column chromatography (SiO2; 0-50% ethyl acetate/petrol) to yield 5-[(3-fluorobenzyl)sulfanyl]-2,3-bis(methoxymethoxy)pyridine (690 mg, 64%).

Workup

stirringthe reaction mixture stirred for 3 hours
temperatureUpon warming to room temperature the reaction mixture
customwas partitioned between dichloromethane and water
extractionThe aqueous phase was re-extracted
washthe combined organic extracts were washed with brine
customdried
concentrationconcentrated in vacuo
customThe crude product was purified by column chromatography (SiO2; 0-50% ethyl acetate/petrol)

Sources & evidence

ORD record: ord-1d74c1994d6e417f9901a7fcba634942
Source dataset: uspto-grants-2015_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09180122B2

Reaction notes

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