Acetic Acid → 2-(1-Trityl-1H-tetrazol-5-YL)phenylboronic acid

HRID 447229

Reaction equation

HRID 447229 reaction equation
[C:1]1([C:7]2[N:11]([C:12]([C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)[C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=3)[N:10]=[N:9][N:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[B:31](OC(C)C)([O:36]C(C)C)[O:32]C(C)C.CC(O)=O>C1COCC1>[C:12]([N:11]1[C:7]([C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=2[B:31]([OH:36])[OH:32])=[N:8][N:9]=[N:10]1)([C:25]1[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=1)([C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)[C:19]1[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=1

Participants

5

Reactant 3

HCID 176Acetic AcidHCID 21531Triisopropyl borateHCID 104303585-phenyl-1-trityl-1H-tetrazole

Product 1

HCID 103427452-(1-Trityl-1H-tetrazol-5-YL)phenylboronic acidYield 69.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-25 °C

Procedure

A solution of 5-phenyl-1-trityl-1H-tetrazole (70.0 g, 180.2 mmol, 1.0 equiv) in THF (dried) (560 mL) was placed in a flask that had been purged and maintained with an inert atmosphere of nitrogen. The mixture was cooled to −25° C. Butyllithium was added to quench the trace of water in the reaction mixture until the color of the mixture remained red for at least 5 minutes. Butyllithium (80.0 mL, 2.5 mol/L) was then added dropwise to the mixture over a period of about 40 minutes at a temperature below −25° C. The temperature of the mixture was raised to −5° C., and the mixture was stirred at −5° C. for 3 hours. The mixture was then cooled to −25° C. and triisopropyl borate (50.8 g, 270.1 mmol, 1.5 equiv) was added dropwise. The mixture was warmed to temperature in the range of 25-35° C. and stirred for 2 hours. The mixture was cooled again in the range of 0-5° C., and 3% aqueous AcOH (470 mL) was slowly added over 30-40 minutes. The mixture was stirred for 30-40 minutes and then filtered. The crude product was washed with water (2×300 mL) and dried over reduced pressure. The crude product was then purified by re-crystallization from EtOAc (1 g/15 ml) to yield 2-(1-trityl-1H-tetrazol-5-yl)phenylboronic acid (54 g) as a white solid. ES m/z: [M+H]+ calcd for C26H21BN4O2, 433.1, found 433.1.

Workup

  1. customthat had been purged
  2. temperaturemaintained with an inert atmosphere of nitrogen
  3. additionButyllithium was added
  4. customto quench the trace of water in the reaction mixture until the color of the mixture
  5. waitremained red for at least 5 minutes
  6. additionButyllithium (80.0 mL, 2.5 mol/L) was then added dropwise to the mixture over a period of about 40 minutes at a temperature below −25° C
  7. temperatureThe temperature of the mixture was raised to −5° C.
  8. temperatureThe mixture was then cooled to −25° C.
  9. temperatureThe mixture was warmed to temperature in the range of 25-35° C.
  10. stirringstirred for 2 hours
  11. additionwas slowly added over 30-40 minutes
  12. stirringThe mixture was stirred for 30-40 minutes
  13. filtrationfiltered
  14. washThe crude product was washed with water (2×300 mL)
  15. customdried over reduced pressure
  16. customThe crude product was then purified by re-crystallization from EtOAc (1 g/15 ml)

Sources & evidence

ORD record
ord-0c8a2c4c5eee473a9f3714eab57a7513
Source dataset
uspto-grants-2013_07
Patent number
US08481549B2

Linked notes

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