Hydrochloric Acid → 2-(Tert-butyldimethylsilanyloxymethyl)-4-fluoro-5-trimethylsilanylfuran-3-yl-boronic acid

HRID 1778415Notes

Reaction equation

HRID 1778415 reaction equation
[C:1]([Si:5]([O:8][CH2:9][C:10]1[O:11][CH:12]=[C:13]([F:15])[CH:14]=1)([CH3:7])[CH3:6])([CH3:4])([CH3:3])[CH3:2].C([Li])CCC.Cl[Si:22]([CH3:25])([CH3:24])[CH3:23].[B:26](OC(C)C)([O:31]C(C)C)[O:27]C(C)C.Cl>C1COCC1.C(OCC)C>[Si:5]([O:8][CH2:9][C:10]1[O:11][C:12]([Si:22]([CH3:25])([CH3:24])[CH3:23])=[C:13]([F:15])[C:14]=1[B:26]([OH:31])[OH:27])([C:1]([CH3:4])([CH3:2])[CH3:3])([CH3:7])[CH3:6]

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 6397ChlorotrimethylsilaneHCID 21531Triisopropyl borateHCID 59648516Furan, 2-[[[(1,1-diMethylethyl)diMethylsilyl]oxy]Methyl]-4-fluoro-HCID 178418339Butyllithium2×

Product 1

HCID 666863202-(Tert-butyldimethylsilanyloxymethyl)-4-fluoro-5-trimethylsilanylfuran-3-yl-boronic acidYield 59.2%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

tert-Butyl-(4-fluorofuran-2-ylmethoxy)dimethylsilane (prepared according to Heffernan et al, US2008 0058395, 6.75 g) was dissolved in anhydrous THF (100 mL), under an atmosphere of nitrogen and cooled to −78° C. n-Butyllithium (2.5M in hexanes, 11.74 mL) was added and the mixture was stirred at −78° C. for 10 minutes. Chlorotrimethylsilane (3.19 g) was added and the mixture was stirred at −78° C. for 40 minutes. Further n-butyllithium (2.5M in hexanes, 11.74 mL) was added and the mixture was stirred at −78° C. for 40 minutes, before triisopropyl borate (11.04 g) was added. The resultant mixture was stirred at −78° C. for 5 minutes then allowed to warm to room temperature. 1M aqueous hydrochloric acid (100 mL) and diethyl ether (50 mL) were added and the mixture was stirred vigorously for 5 minutes. The layers were separated and the organic layer was dried (MgSO4) and filtered. The filtrate was concentrated in vacuo and the residue was purified by chromatography on silica, eluting with a mixture of ethyl acetate and cyclohexane, with a gradient of 0-20% to give 2-(tert-butyldimethylsilanyloxymethyl)-4-fluoro-5-trimethylsilanylfuran-3-yl-boronic acid (6.01 g) as a brown oil which was used without further characterisation.

Workup

  1. additionwas added
  2. stirringthe mixture was stirred at −78° C. for 40 minutes
  3. additionwas added
  4. temperatureto warm to room temperature
  5. stirringthe mixture was stirred vigorously for 5 minutes
  6. customThe layers were separated
  7. dry with materialthe organic layer was dried (MgSO4)
  8. filtrationfiltered
  9. concentrationThe filtrate was concentrated in vacuo
  10. customthe residue was purified by chromatography on silica
  11. washeluting with a mixture of ethyl acetate and cyclohexane, with a gradient of 0-20%

Sources & evidence

ORD record
ord-2cdc9f18c127494d8d901a1e8bc7014f
Source dataset
uspto-grants-2016_02
Patent number
US09266896B2

Reaction notes

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