Triisopropyl borate → 3-cyano-1-cyclobutyl-6-cyclopropyl-1H-indol-2-ylboronic acid
Reaction equation
[CH:1]1([N:6]2[C:14]3[C:9](=[CH:10][C:11](F)=[C:12]([CH3:15])[CH:13]=3)[C:8]([C:17]#[N:18])=[CH:7]2)[CH2:5][CH2:4][CH2:3]C1.[B:19](OC(C)C)([O:24]C(C)C)[O:20]C(C)C.[Li+].[CH3:33][CH:34]([N-]C(C)C)C>C1COCC1>[C:17]([C:8]1[C:9]2[C:14](=[CH:13][C:12]([CH:15]3[CH2:34][CH2:33]3)=[CH:11][CH:10]=2)[N:6]([CH:1]2[CH2:3][CH2:4][CH2:5]2)[C:7]=1[B:19]([OH:24])[OH:20])#[N:18]Participants
5
Conditions
- Temperature
- -78 °C
Procedure
Into a solution of 1-cyclopentyl-5-fluoro-6-methyl-1H-indole-3-carbonitrile (4.4 g, 18.2 mmol) and triisopropyl borate (7.6 mL, 33 mmol) in THF (75 mL) at −78° C. was added LDA (1.5 M in cyclohexane, 15.8 mL, 23.7 mmol). The mixture was stirred at −78° C. for 30 min, quenched with ice water (200 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 aq. 2 N HCl to pH 5 and then extracted with CH2Cl2 (100 mL). The organic layer was dried over Na2SO4 and concentrated to give 3-cyano-1-cyclobutyl-6-cyclopropyl-1H-indol-2-ylboronic acid as a solid (6.2 g, 90% pure by LCMS) which was used in the next step without further purification.
Workup
- customquenched with ice water (200 mL)
- stirringstirred for 15 min
- temperaturewithout cooling
- extractionThe mixture was extracted with ethyl acetate 1:1 in hexane (20 mL)
- extractionextracted with CH2Cl2 (100 mL)
- dry with materialThe organic layer was dried over Na2SO4
- concentrationconcentrated
Sources & evidence
- ORD record
- ord-fee8d33d798d46e09ba7d37b41fd15ea
- Source dataset
- uspto-grants-2014_05
- Patent number
- US08735414B2
Reaction notes
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