Acetone → 4-(2-Hydroxypropan-2-yl)-3-methoxybenzoic acid

HRID 2204179Notes

Reaction equation

Br[C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=[O:7])=[CH:4][C:3]=1[O:11][CH3:12].[Li]CCCC.[CH3:18][C:19]([CH3:21])=[O:20].Cl>C1COCC1.[OH-].[Na+]>[OH:20][C:19]([C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=[O:7])=[CH:4][C:3]=1[O:11][CH3:12])([CH3:21])[CH3:18]

Participants

Conditions

Temperature: -78 °C

Procedure

4-Bromo-3-methoxy-benzoic acid (2.00 g, 8.67 mmol) was dissolved in THF (50 mL) and the solution was cooled to −78° C. n-BuLi in hexanes (7.6 mL of 2.5 M, 19 mmol) was added dropwise over 15 minutes. The reaction mixture was allowed to stir for 30 minutes at −78° C. and then acetone (640 μL, 8.9 mmol) was added in a dropwise manner. The reaction mixture was allowed to stir for 30 minutes at −78° C., and then it was allowed to warm to room temperature. 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 utilizing a gradient of 0-5% methanol in dichloromethane to give 4-(2-hydroxypropan-2-yl)-3-methoxybenzoic acid (618 mg, 34%). ESI-MS m/z calc. 210.1, found 209.1 (M−1)−; Retention time: 0.68 minutes (3 min run).

Workup

additionwas added dropwise over 15 minutes
stirringto stir for 30 minutes at −78° C.
temperatureto warm to room temperature
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-dbc31e2316f949ed8886e5954e437464
Source dataset: uspto-grants-2016_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09365588B2

Reaction notes

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