1-(Bromomethyl)-3-chlorobenzene → 5-(3-Chlorobenzylthio)-2,3-dimethoxypyridine

HRID 709023Notes

Reaction equation

[CH3:1][O:2][C:3]1[CH:4]=[C:5]([S:11][CH2:12][CH2:13][C:14](OC)=O)[CH:6]=[N:7][C:8]=1[O:9][CH3:10].CC(C)([O-])C.[K+].BrC[C:26]1C=C[CH:29]=[C:28]([Cl:32])[CH:27]=1>C1COCC1>[Cl:32][C:28]1[CH:29]=[C:13]([CH:14]=[CH:26][CH:27]=1)[CH2:12][S:11][C:5]1[CH:4]=[C:3]([O:2][CH3:1])[C:8]([O:9][CH3:10])=[N:7][CH:6]=1

Participants

Conditions

Temperature: -45 °C

Procedure

To a cooled solution of methyl 3-[(5,6-dimethoxypyridin-3-yl)sulfanyl]propanoate (Intermediate 7, 257 mg, 1 mmol) in THF (6 ml) at −45° C. was added potassium tert-butoxide (123 mg, 1.10 mmol). After stirring at −45° C. for 20 minutes, 1-(bromomethyl)-3-chlorobenzene (0.16 ml, 1.20 mmol) was added and the reaction mixture was stirred with warming to room temperature for 2 hours. The resulting mixture was partitioned between ethyl acetate (15 ml) and water (15 nil) and the resulting organic layer was washed with brine (15 ml), dried (MgSO4), filtered and concentrated in vacuo to give yellow oil. Purification by column chromatography (SiO2; 0-10% ethyl acetate in petrol) gave 5-(3-chlorobenzylthio)-2,3-dimethoxypyridine as a yellow oil (244 mg, 82%).

Workup

stirringthe reaction mixture was stirred
temperaturewith warming to room temperature for 2 hours
customThe resulting mixture was partitioned between ethyl acetate (15 ml) and water (15 nil)
washthe resulting organic layer was washed with brine (15 ml)
dry with materialdried (MgSO4)
filtrationfiltered
concentrationconcentrated in vacuo
customto give yellow oil
customPurification by column chromatography (SiO2; 0-10% ethyl acetate in petrol)

Sources & evidence

ORD record: ord-000d5a632ec344d18fa7c269f746add2
Source dataset: uspto-grants-2015_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09180122B2

Reaction notes

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