Hydrochloric Acid → 4-(Isopropylthio)-3-methylbenzoic acid

HRID 1908112

Reaction equation

C([Li])CCC.Br[C:7]1[CH:15]=[CH:14][C:10]([C:11]([OH:13])=[O:12])=[CH:9][C:8]=1[CH3:16].[CH:17]([S:20]SCCC)([CH3:19])[CH3:18].Cl>C1COCC1.[OH-].[Na+]>[CH:17]([S:20][C:7]1[CH:15]=[CH:14][C:10]([C:11]([OH:13])=[O:12])=[CH:9][C:8]=1[CH3:16])([CH3:19])[CH3:18]

Participants

Conditions

Temperature: -78 °C

Procedure

Butyllithium (16 mL of 1.6 M, 26 mmol) was added drop-wise to a mixture of 4-bromo-3-methyl-benzoic acid (2.5 g, 12 mmol) and THF (63 mL) at −78° C. The mixture was allowed to stir at −78° C. for 30 minutes before a solution of 2-isopropyldisulfanylpropane (1.7 g, 12 mmol) in THF (2 mL) was added drop-wise. The mixture was allowed to stir at −78° C. for 30 min, then 30 min at rt. The reaction mixture was then diluted with 100 mL of 1M aqueous sodium hydroxide. The organic layer was discarded and the aqueous layer was made acidic with 4M aqueous hydrochloric acid. The aqueous layer was then extracted 3 times with ethyl acetate. The combined extracts were dried over sodium sulfate and then evaporated to dryness. The crude material was purified by column chromatography using a gradient of 0-5% MeOH in dichloromethane to give 4-(isopropylthio)-3-methylbenzoic acid (870 mg, 18%). MS m/z calc. 210.3. found 211.2 (M+1)+. Retention time: 2.32 minutes (3 min run).

Workup

additionwas added drop-wise
custom30 min
customat rt
extractionThe aqueous layer was then extracted 3 times with ethyl acetate
dry with materialThe combined extracts were dried over sodium sulfate
customevaporated to dryness
customThe crude material was purified by column chromatography

Sources & evidence

ORD record: ord-15b5c7efc57445d69a13ce7d01647e70
Source dataset: uspto-grants-2013_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08598164B2

Linked notes

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