Triisopropyl borate → 3-cyano-1-cyclobutyl-6-(difluoromethoxy)-1H-indol-2-ylboronic acid
Reaction equation
[CH:1]1([N:5]2[C:13]3[C:8](=[CH:9][CH:10]=[C:11]([O:14][CH:15]([F:17])[F:16])[CH:12]=3)[C:7]([C:18]#[N:19])=[CH:6]2)[CH2:4][CH2:3][CH2:2]1.[B:20](OC(C)C)([O:25]C(C)C)[O:21]C(C)C.[Li+].CC([N-]C(C)C)C>C1COCC1>[C:18]([C:7]1[C:8]2[C:13](=[CH:12][C:11]([O:14][CH:15]([F:16])[F:17])=[CH:10][CH:9]=2)[N:5]([CH:1]2[CH2:2][CH2:3][CH2:4]2)[C:6]=1[B:20]([OH:25])[OH:21])#[N:19]Participants
5
Conditions
- Temperature
- -78 °C
Procedure
Into a solution of 1-cyclobutyl-6-(difluoromethoxy)-1H-indole-3-carbonitrile (1.5 g, 5.7 mmol) and triisopropyl borate (2.4 mL, 10.3 mmol) in THF (25 mL) at −78° C. was added LDA (1.5 M in cyclohexane, 5.0 mL, 7.5 mmol). The mixture was stirred at −78° C. for 30 min and then quenched with ice water (60 mL) and stirred for 15 min without cooling. The mixture was extracted with ethyl acetate 1:1 in hexane (20 mL). The aqueous layer was acidified with 2 N aq. HCl to pH 5 and extracted with CH2Cl2 (60 mL). The organic layer was dried over Na2SO4 and concentrated to give 3-cyano-1-cyclobutyl-6-(difluoromethoxy)-1H-indol-2-ylboronic acid as a solid (1.8 g, 60% pure by LCMS) that was used in the next step without further purification.
Workup
- customquenched with ice water (60 mL)
- stirringstirred for 15 min
- temperaturewithout cooling
- extractionThe mixture was extracted with ethyl acetate 1:1 in hexane (20 mL)
- extractionextracted with CH2Cl2 (60 mL)
- dry with materialThe organic layer was dried over Na2SO4
- concentrationconcentrated
Sources & evidence
- ORD record
- ord-db858bfe152d4ebb8df9ce785d809e38
- Source dataset
- uspto-grants-2014_05
- Patent number
- US08735414B2
Reaction notes
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