2-Isopropoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolane → 7-Fluoro-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-(triisopropylsilyl)-1H-indole

HRID 923686Notes

Reaction equation

HRID 923686 reaction equation
[F:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:10]=1[N:9]([Si:11]([CH:18]([CH3:20])[CH3:19])([CH:15]([CH3:17])[CH3:16])[CH:12]([CH3:14])[CH3:13])[CH:8]=[CH:7]2.C([Li])(CC)C.C(O[B:30]1[O:34][C:33]([CH3:36])([CH3:35])[C:32]([CH3:38])([CH3:37])[O:31]1)(C)C>C1COCC1>[F:1][C:2]1[C:3]([B:30]2[O:34][C:33]([CH3:36])([CH3:35])[C:32]([CH3:38])([CH3:37])[O:31]2)=[CH:4][CH:5]=[C:6]2[C:10]=1[N:9]([Si:11]([CH:15]([CH3:17])[CH3:16])([CH:18]([CH3:20])[CH3:19])[CH:12]([CH3:13])[CH3:14])[CH:8]=[CH:7]2

Participants

5

Reactant 3

HCID 50177412-Isopropoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolaneHCID 114930397-Fluoro-1-(triisopropylsilyl)-1H-indoleHCID 178418400CID 53628100

Product 1

HCID 904186597-Fluoro-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-(triisopropylsilyl)-1H-indoleYield 73%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-75 °C

Procedure

7-Fluoro-1-(triisopropylsilyl)-1H-indole (4.0 g, 14 mmol) (Prepared according to M. Schlosser, et al, Eur. J. Org. Chem. 2006, 2956-2969) was dissolved in 30 mL dry THF, cooled to −75° C., treated in portions with sec-butyl lithium (10 mL, 1.4 M, 14 mmol) and stirred for 2 h at −75° C. 2-Isopropoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (3.0 mL, 2.7 g, 14 mmol) was added in portions and the mixture was stirred for 1 h at −75° C. The cooling was removed and the temperature was allowed to rise to 5° C. over 30 min. The reaction was quenched by addition of 5 mL sat. NH4Cl and partitioned between ethyl acetate and water. The organic phase was washed with sat. NaCl, dried (Na2SO4), evaporated onto silica gel, and purified by flash chromatography (SiO2; eluting with hexanes) to give 4.2 g of the title compound as a thick oil (4.2 g, 73%): 1H NMR (400 MHz, CDCl3) δ 7.43 (dd, J=7.9, 4.6 Hz, 1H), 7.38 (m, 2H), 1.75 (m, 3H), 1.38 (s, 12H), 1.13 (d, J=7.6 Hz, 18H). 19F NMR (376 MHz, CDCl3) δ −113.07. EIMS m/z 417.

Workup

  1. stirringthe mixture was stirred for 1 h at −75° C
  2. customThe cooling was removed
  3. waitto rise to 5° C. over 30 min
  4. customThe reaction was quenched by addition of 5 mL sat. NH4Cl
  5. custompartitioned between ethyl acetate and water
  6. washThe organic phase was washed with sat. NaCl
  7. dry with materialdried (Na2SO4)
  8. customevaporated onto silica gel
  9. custompurified by flash chromatography (SiO2; eluting with hexanes)

Sources & evidence

ORD record
ord-64edb2bc28a44080b40d5c83ae90fdf3
Source dataset
uspto-grants-2016_03
Patent number
US09278985B2

Reaction notes

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