Hydrochloric Acid → 1-(3-(Chloromethyl)phenyl)-2-hydroxy-2-methylpropan-1-one

HRID 402972

Reaction equation

[OH:1][C:2]([CH3:12])([CH3:11])[C:3]([C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)=[O:4].[Al+3].[Cl-:14].[Cl-].[Cl-].[CH2:17]=O.Cl.[OH-].[Na+]>C(Cl)(Cl)Cl.O>[Cl:14][CH2:17][C:7]1[CH:6]=[C:5]([C:3](=[O:4])[C:2]([OH:1])([CH3:12])[CH3:11])[CH:10]=[CH:9][CH:8]=1

Participants

Conditions

Temperature: 4 °C

Procedure

under nitrogen atmosphere 5 grams of Darocur 1173 (2-hydroxy-2-methyl-1-phenylpropan-1-one) was mixed with 24 grams of anhydrous AlCl3 in 100 mL of dry chloroform. Upon cooling to 4° C. 4.5 grams of paraformaldehyde powder was slowly added and the resultant mixture was stirred at room temperature for 12 hrs (note that HCl gas released from the reaction was neutralized by 2N NaOH solution). The mixture was poured into water, and the precipitate generated was dissolved by adding 2N HCl solution. The organic layer thus separated was collected, and the aqueous layer was extracted with ethyl acetate for three times. The combined chloroform and ethyl acetate layer was next dried over anhydrous Na2SO4, filtered, and concentrated. The residue was loaded onto silica gel column and eluted by mixtures of hexane/ethyl acetate (V/V=15/1) to give the intermediate 1-(3-(chloromethyl)phenyl)-2-hydroxy-2-methylpropan-1-one as a light-yellow oil (33% yield).

Workup

dissolutionthe precipitate generated was dissolved
customThe organic layer thus separated
customwas collected
extractionthe aqueous layer was extracted with ethyl acetate for three times
dry with materialThe combined chloroform and ethyl acetate layer was next dried over anhydrous Na2SO4
filtrationfiltered
concentrationconcentrated
washeluted by mixtures of hexane/ethyl acetate (V/V=15/1)

Sources & evidence

ORD record: ord-61a130eaae824248a8fd964ff58c0a7c
Source dataset: uspto-grants-2014_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08742175B2

Linked notes

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