Methanesulfonic Acid → 3-Bromo-6-fluoro-2-methylbenzonitrile
Reaction equation
[F:1][C:2]1[CH:9]=[CH:8][CH:7]=[C:6]([CH3:10])[C:3]=1[C:4]#[N:5].S(O)(C)(=O)=O.C1C(=O)N([Br:23])C(=O)C1>>[Br:23][C:7]1[C:6]([CH3:10])=[C:3]([C:2]([F:1])=[CH:9][CH:8]=1)[C:4]#[N:5]Participants
Conditions
- Temperature
- 50 °C
Procedure
To a 3 L 3 Neck round bottomed flask equipped with overhead stirrer was charged 2-Fluoro-6-methyl-benzonitrile (191.8 g., 1419 mmol) and MsOH (563 mL, 8516 mmol). NBS (265 g., 1490 mmol) was added portionwise to this stirred solution over 30 minutes, and the mixture was stirred at 50° C. for 33 hours. By that time, HPLC showed the reaction to be mostly complete, so the reaction was poured into 1 L of ice (exotherm noted), diluted with 700 mL 30% EtOAc/Hexanes, and agitated. The aqueous layer was cut, and the organics washed 2× with 1N NaOH and with water. The aqueous cuts were observed to be significantly enriched with impurities. The organics were dried over MgSO4, concentrated, then stored in a −10° C. freezer overnight. Precipitate formed over this time, and was filtered and washed with 5% EtOAc/Hexanes, providing a first crop of product. A second crop of precipitate provided further 3-Bromo-6-fluoro-2-methyl-benzonitrile.
Workup
- customthe reaction
- stirringagitated
- washthe organics washed 2× with 1N NaOH
- dry with materialThe organics were dried over MgSO4
- concentrationconcentrated
- waitstored in a −10° C. freezer overnight
- customPrecipitate formed over this time
- filtrationwas filtered
- washwashed with 5% EtOAc/Hexanes
- customproviding a first crop of product
Sources & evidence
- ORD record
- ord-3854043021ad43c5b2c600bede9e1bd9
- Source dataset
- uspto-grants-2015_12
- Patent number
- US09206199B2
Reaction notes
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