Ammonium Chloride → (4-Bromophenyl)(thiophen-2-yl)methanone

HRID 2251649Notes

Reaction equation

[Br:1][C:2]1[CH:13]=[CH:12][C:5]([C:6](N(OC)C)=[O:7])=[CH:4][CH:3]=1.[S:14]1[CH:18]=[CH:17][CH:16]=[C:15]1[Li].[Cl-].[NH4+]>C1COCC1>[Br:1][C:2]1[CH:13]=[CH:12][C:5]([C:6]([C:15]2[S:14][CH:18]=[CH:17][CH:16]=2)=[O:7])=[CH:4][CH:3]=1

Participants

Conditions

Temperature: 0 °C

Procedure

To a stirred solution of 4-bromobenzoyl chloride (20.0 g, 91.1 mmol) in dichloromethane (300 mL) at −78° C. was added triethylamine (28.0 mL, 200.0 mmol), and O,N-dimethylhydroxylamine hydrochloride (9.33 g, 95.6 mmol). The resulting solution was allowed to warm to room temperature, stirred for 1.5 hours, and then concentrated. The residue was triturated in acetone and the resulting solid was dissolved in ethyl acetate washed with water and brine. The organic layer was dried over magnesium sulfate, filtered, and concentrated to give 4-bromo-N-methoxy-N-methylbenzamide (18.6 g, 84%). To a solution of 4-bromo-N-methoxy-N-methylbenzamide (3.0 g, 12.29 mmol) in THF (30 mL) at 0° C. under nitrogen was added 2-thienyllithium (1.0 M in THF, 15 mL, 15 mmol) slowly over 10 minutes. The solution was stirred at 0° C. for 1 hour, poured into a saturated aqueous ammonium chloride solution (150 mL), and extracted several times with ethyl acetate. The combined organic layers were dried over magnesium sulfate, filtered, and concentrated. The residue was triturated with ether to give (4-bromophenyl)(thien-2-yl)methanone as a brown solid (1.1 g, 34%). MS (ES) m/z 266.9.

Workup

extractionextracted several times with ethyl acetate
dry with materialThe combined organic layers were dried over magnesium sulfate
filtrationfiltered
concentrationconcentrated
customThe residue was triturated with ether

Sources & evidence

ORD record: ord-82328d53dd324a98b2ca1efb0d4631c9
Source dataset: uspto-grants-2008_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07319152B2

Reaction notes

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