Hydrochloric Acid → 2-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)thieno[3,2-c]pyridine

HRID 2424761Notes

Reaction equation

HRID 2424761 reaction equation
[S:1]1[C:9]2[CH:8]=[CH:7][N:6]=[CH:5][C:4]=2[CH:3]=[CH:2]1.C([Li])CCC.[B:15]([O:24][CH:25]([CH3:27])[CH3:26])([O:20][CH:21]([CH3:23])[CH3:22])OC(C)C.OC(C(O)(C)C)(C)C.Cl>O1CCCC1.C(OCC)C.O1CCOCC1>[CH3:27][C:25]1([CH3:26])[C:21]([CH3:22])([CH3:23])[O:20][B:15]([C:2]2[S:1][C:9]3[CH:8]=[CH:7][N:6]=[CH:5][C:4]=3[CH:3]=2)[O:24]1

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 6425PinacolHCID 21531Triisopropyl borateHCID 67500Thieno(3,2-c)pyridineHCID 178418339Butyllithium

Product 1

HCID 533986132-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)thieno[3,2-c]pyridineYield 82.7%

Reagents, catalysts & solvents 3

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
-72.5 °C

Procedure

To a −70° C. solution of thieno[3,2-c]pyridine (21.6 g) in 400 mL of dry tetrahydrofuran under nitrogen gas was added n-butyl lithium (99.9 ml of a 1.6 molar solution in hexanes) over about 15-20 minutes keeping the temperature below −65° C. The solution became cloudy and dark brown. After 45 minutes tri-isopropyl borate (33.06 g) was added and the mixture became homogeneous. The mixture was stirred at −70 to −75° C. for 2 hours. The mixture was allowed to warm to −30° C., then a solution of pinacol in 100 mL of diethyl ether was added over 4 minutes. The reaction mixture became an orange homogeneous solution. The temperature was allowed to warm to 5° C. and held at that temperature for 1 hour. The reaction mixture was neutralized (pH 7) very slowly with 40 mL of 4M hydrochloric acid in 1,4-dioxane, keeping the temperature below 10° C. A precipitate formed. The reaction mixture was stirred for 1 hour and then the solid was collected by filtration. The solid was dried under vacuum at 40° C. for 16 hours. The dry solid (36 g) was stirred with 400 mL of water for 1.5 hours. The slurry was filtered and the solid collected. The solid was dried under a flow of air for 60 hours to give the desired product (34.5 g). 1H NMR (400 MHz, Chloroform-d) δ ppm 1.21 (s, 12 H) 7.66-7.70 (m, 1 H) 7.80 (d, J=0.78 Hz, 1 H) 8.28 (d, J=5.65 Hz, 1 H) 8.98 (d, J=0.97 Hz, 1 H).

Workup

  1. customthe temperature below −65° C
  2. temperatureto warm to −30° C.
  3. temperatureto warm to 5° C.
  4. waitheld at that temperature for 1 hour
  5. customthe temperature below 10° C
  6. customA precipitate formed
  7. stirringThe reaction mixture was stirred for 1 hour
  8. filtrationthe solid was collected by filtration
  9. customThe solid was dried under vacuum at 40° C. for 16 hours
  10. stirringThe dry solid (36 g) was stirred with 400 mL of water for 1.5 hours
  11. filtrationThe slurry was filtered
  12. customthe solid collected
  13. customThe solid was dried under a flow of air for 60 hours

Sources & evidence

ORD record
ord-aca8fecb25594fe38fcc5534e93f0a46
Source dataset
uspto-grants-2011_06
Patent number
US07964612B2

Reaction notes

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