Hydrochloric Acid → HCID 67439098, compound

HRID 1483766Notes

Reaction equation

HRID 1483766 reaction equation
C([C:3]1[CH:4]=[C:5]([CH:15]=[CH:16][C:17]=1[B:18]1[O:22]C(C)(C)[C:20]([CH3:26])(C)[O:19]1)[O:6][C:7]1[CH:14]=[CH:13][C:10]([C:11]#[N:12])=[CH:9][N:8]=1)=O.C[Mg+].[Br-].Cl.C([O-])(O)=O.[Na+]>C1COCC1.O>[OH:22][B:18]1[C:17]2[CH:3]=[CH:4][C:5]([O:6][C:7]3[CH:14]=[CH:13][C:10]([C:11]#[N:12])=[CH:9][N:8]=3)=[CH:15][C:16]=2[CH:20]([CH3:26])[O:19]1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 516892Sodium BicarbonateHCID 86636422HCID 86636422, compoundHCID 178418689HCID 178418689, compound

Product 1

HCID 67439098HCID 67439098, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a suspension of 6-[3-formyl-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenoxy]-nicotinonitrile (105 mg, 0.3 mmol, 1.0 eq.) in THF (5.0 mL) at 0° C. was added MeMgBr (0.15 mL, 0.45 mmol, 1.5 eq.) drop wise. The mixture was stirred at 0° C. for 20 minutes and allowed to warm to room temperature in another 1 h. After cooling to 0° C., the clear solution was carefully treated with H2O (1 mL), followed by slow addition of HCl (10 mL, 3N). The resulting yellow suspension was allowed to ward to room temperature gradually and stirred for 2 h. The mixture was then treated with sat. NaHCO3 drop wise until PH reaching 1 and was extracted with EtOAc (3×10 mL). Combined organic extracts was washed with brine (10 mL), dried over MgSO4, filtered and the filtrate was concentrated under reduced pressure. The residue was applied to silica chromatography eluting with MeOH/DCM (0:100 to 10:90) to give 6-(1-hydroxy-3-methyl-1,3-dihydro-benzo[c][1,2]oxaborol-5-yloxy)-nicotinonitrile as a white solid. LCMS (m/z) 267 (M+H); 1H NMR (DMSO-d6) δ: 9.19 (s, 1H), 8.71 (dd, J=2.3, 0.6 Hz, 1H), 8.38 (dd, J=8.7, 2.4 Hz, 1H), 7.80 (d, J=7.9 Hz, 1H), 7.28-7.35 (m, 2H), 7.20 (dd, J=7.9, 2.0 Hz, 1H), 5.26 (q, J=6.5 Hz, 1H), 1.45 (d, J=6.6 Hz, 3H).

Workup

  1. temperatureto warm to room temperature in another 1 h
  2. temperatureAfter cooling to 0° C.
  3. customto ward to room temperature
  4. stirringstirred for 2 h
  5. extractionwas extracted with EtOAc (3×10 mL)
  6. washCombined organic extracts was washed with brine (10 mL)
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. concentrationthe filtrate was concentrated under reduced pressure
  10. washeluting with MeOH/DCM (0:100 to 10:90)

Sources & evidence

ORD record
ord-a078ac9ca28c46bcaad83529b37e9bf2
Source dataset
uspto-grants-2016_08
Patent number
US09416146B2

Reaction notes

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