Hydrochloric Acid → HCID 67440495, compound

HRID 1471562Notes

Reaction equation

HRID 1471562 reaction equation
[F:1][C:2]1[C:18]([CH:19]=O)=[C:17]([B:21]2[O:25]C(C)(C)C(C)(C)[O:22]2)[CH:16]=[CH:15][C:3]=1[O:4][C:5]1[CH:12]=[CH:11][C:8]([C:9]#[N:10])=[C:7]([O:13][CH3:14])[N:6]=1.[BH4-].[Na+].Cl>CO>[F:1][C:2]1[C:18]2[CH2:19][O:22][B:21]([OH:25])[C:17]=2[CH:16]=[CH:15][C:3]=1[O:4][C:5]1[CH:12]=[CH:11][C:8]([C:9]#[N:10])=[C:7]([O:13][CH3:14])[N:6]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 4311764Sodium borohydride3×HCID 86636443HCID 86636443, compound

Product 1

HCID 67440495HCID 67440495, compoundYield 20.1%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
0 °C

Procedure

A solution of 6-(2-fluoro-3-formyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy)-2-methoxynicotinonitrile (1.45 g, 3.64 mmol) in methanol (15 mL) was put on an ice water bath. Sodium borohydride was added in portions. The reaction was stirred at 0° C. for five minutes and then stirred at room temperature for 2 hours. The reaction was cooled again to 0° C. on an ice water bath and sodium borohydride (0.034 g, 0.91 mmol) was added. The reaction was stirred at room temperature for 1 hour. The reaction was again cooled to 0° C. and sodium borohydride (0.034 g, 0.91 mmol) was again added. The reaction was stirred at room temperature for one hour. The reaction was neutralized to pH 6 to 7 using 1 M HCl. The solution was then extracted using ethyl acetate and 0.5 M boronic acid solution in water. The organic layer was washed two more times with the 0.5 M boronic acid solution, then washed with brine, dried over anhydrous sodium sulfate, and filtered. The solvent was removed under reduced pressure. The residue was purified by silica gel column using Combiflash to give 6-(4-fluoro-1-hydroxy-1,3-dihydrobenzo[c][1,2]oxaborol-5-yloxy)-2-methoxynicotinonitrile (0.220 g, 20% yield). ES(−) MS m/z=300 (M−H)−; 1H NMR (400 MHz, DMSO-d6) δ ppm 3.67 (s, 3 H), 5.11 (s, 2 H), 6.82 (d, J=8.2 Hz, 1 H), 7.39 (t, J=6.8, J=7.5 Hz, 1 H), 7.60 (d, J=7.8 Hz, 1 H), 8.28 (d, J=8.2 Hz, 1 H), 9.47 (s, 1 H).

Workup

  1. stirringstirred at room temperature for 2 hours
  2. temperatureThe reaction was cooled again to 0° C. on an ice water bath
  3. stirringThe reaction was stirred at room temperature for 1 hour
  4. temperatureThe reaction was again cooled to 0° C.
  5. stirringThe reaction was stirred at room temperature for one hour
  6. extractionThe solution was then extracted
  7. washThe organic layer was washed two more times with the 0.5 M boronic acid solution
  8. washwashed with brine
  9. dry with materialdried over anhydrous sodium sulfate
  10. filtrationfiltered
  11. customThe solvent was removed under reduced pressure
  12. customThe residue was purified by silica gel column

Sources & evidence

ORD record
ord-37cc60ffee284dadb50fecc5e9e0759f
Source dataset
uspto-grants-2015_04
Patent number
US09012431B2

Reaction notes

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