Hydrochloric Acid → (1-(tert-Butoxycarbonyl)-4-fluoro-1H-indol-2-yl)boronic acid

HRID 1776941Notes

Reaction equation

HRID 1776941 reaction equation
C(NC(C)C)(C)C.[Li]CCCC.[F:13][C:14]1[CH:22]=[CH:21][CH:20]=[C:19]2[C:15]=1[CH:16]=[CH:17][N:18]2[C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24].[B:30](OC(C)C)([O:35]C(C)C)[O:31]C(C)C.Cl>C1COCC1>[C:26]([O:25][C:23]([N:18]1[C:19]2[C:15](=[C:14]([F:13])[CH:22]=[CH:21][CH:20]=2)[CH:16]=[C:17]1[B:30]([OH:35])[OH:31])=[O:24])([CH3:29])([CH3:28])[CH3:27]

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 7912DiisopropylamineHCID 21531Triisopropyl borateHCID 14710388tert-Butyl 4-fluoro-1H-indole-1-carboxylateHCID 178418339Butyllithium

Product 1

HCID 44118245(1-(tert-Butoxycarbonyl)-4-fluoro-1H-indol-2-yl)boronic acidYield 76.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

To a solution of diisopropylamine (7.5 mL, 0.11 mol) in THF (35 mL) at 0° C. was added n-BuLi (21 mL, 0.055 mol) dropwise. The mixture was stirred at 0° C. for 40 minutes. Then the mixture was cooled to −78° C. Tert-butyl 4-fluoro-1H-indole-1-carboxylate (5 g, 0.02 mol) in THF (13 mL) was added dropwise slowly. After addition, the mixture was stirred at −78° C. for 2 hours. Then triisopropyl borate (3.29 g, 0.03 mol) was added. The mixture was stirred at −78° C. for another 40 minutes. The reaction was monitored using TLC. When the reaction was completed, the mixture was adjusted to pH=6 with 1 N HCl. After extracted with EtOAc (25 mL×3), the combined organic layers were washed with brine (50 mL), dried over Na2SO4, filtered and concentrated in vacuo. The obtained solid was recrystallized with EtOAc and petroleum ether to provide (1-(tert-butoxycarbonyl)-4-fluoro-1H-indol-2-yl)boronic acid (4.5 g, yield: 76.7%, which might be unstable at high temp. work up, store in fridge). 1H-NMR (CDCl3, 400 MHz) δ 7.77 (d, J=8.4 Hz, 1H), 7.57 (s, 1H), 7.44 (s, 2H), 7.24 (m, 1H), 6.90 (m, 1H), 1.66 (s, 9H). MS (M+H)+: 280.

Workup

  1. temperatureThen the mixture was cooled to −78° C
  2. additionAfter addition
  3. stirringthe mixture was stirred at −78° C. for 2 hours
  4. stirringThe mixture was stirred at −78° C. for another 40 minutes
  5. extractionAfter extracted with EtOAc (25 mL×3)
  6. washthe combined organic layers were washed with brine (50 mL)
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customThe obtained solid was recrystallized with EtOAc and petroleum ether

Sources & evidence

ORD record
ord-38aa5c151105418d8d4f79442f276d6f
Source dataset
uspto-grants-2016_02
Patent number
US09265773B2

Reaction notes

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