Sodium Hydroxide → HCID 89906927, compound

HRID 629072Notes

Reaction equation

HRID 629072 reaction equation
O=S(Cl)Cl.[Br:5][C:6]1[CH:7]=[C:8]([CH:12]=[CH:13][C:14]=1[OH:15])[C:9]([OH:11])=O.CCN(C(C)C)C(C)C.[F:25][C:26]([F:36])([F:35])[O:27][C:28]1[CH:34]=[CH:33][C:31]([NH2:32])=[CH:30][CH:29]=1.[OH-].[Na+]>C1(C)C=CC=CC=1.C1COCC1>[Br:5][C:6]1[CH:7]=[C:8]([CH:12]=[CH:13][C:14]=1[OH:15])[C:9]([NH:32][C:31]1[CH:33]=[CH:34][C:28]([O:27][C:26]([F:25])([F:35])[F:36])=[CH:29][CH:30]=1)=[O:11]

Participants

8

Reactant 5

HCID 14798Sodium HydroxideHCID 24386Thionyl ChlorideHCID 81531DiisopropylethylamineHCID 843683-Bromo-4-hydroxybenzoic acidHCID 6008484-(Trifluoromethoxy)aniline

Product 1

HCID 89906927HCID 89906927, compound

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
80 °C

Procedure

SOCl2 (8.41 mL, 115 mmol) was added to a suspension of 3-bromo-4-hydroxybenzoic acid (5 g, 23.04 mmol) in toluene (50 mL) and the RM was stirred at 80° C. for 2.5 h. The solvent was evaporated off under reduced pressure and the residue was dissolved in THF (25 mL). DIPEA (8.05 mL, 46.1 mmol) was added and the RM was cooled to 0° C., treated with a solution of 4-trifluoromethoxyaniline (3.40 mL, 25.3 mmol) in THF (5 mL) and stirred for 1 h. The RM was treated with 4M NaOH (23.04 mL, 92 mmol), heated at 100° C. for 3 h and the solvent was evaporated off under reduced pressure. The residue was treated with aq. HCl (50 mL of 1M), and extracted with TBME/EtOAc (1:1). The combined extracts were washed with sat. aq. NaHCO3 and brine, dried over MgSO4 and the solvent was evaporated off under reduced pressure to give the crude product was purified by flash chromatography (Silica gel column, 100 g, DCM/EtOAc from 0% to 20EtOAc) and crystallized from cyclohexane/DCM to afford the title compound as a beige solid. UPLC-MS (Condition 1) tR=2.70 min, m/z=375.9/377.8 [M+H]+, m/z=374.0/375.9 [M−H]−; 1H-NMR (400 MHz, DMSO-d6) δ ppm 7.05 (d, J=8.6 Hz, 1H) 7.35 (d, J=8.6 Hz, 2H) 7.80-7.90 (m, 3H) 8.17 (d, J=2.2 Hz, 1H) 10.26 (s, 1H) 11.03 (s, 1H).

Workup

  1. customThe solvent was evaporated off under reduced pressure
  2. dissolutionthe residue was dissolved in THF (25 mL)
  3. temperaturethe RM was cooled to 0° C.
  4. stirringstirred for 1 h
  5. temperatureheated at 100° C. for 3 h
  6. customthe solvent was evaporated off under reduced pressure
  7. additionThe residue was treated with aq. HCl (50 mL of 1M)
  8. extractionextracted with TBME/EtOAc (1:1)
  9. washThe combined extracts were washed with sat. aq. NaHCO3 and brine
  10. dry with materialdried over MgSO4
  11. customthe solvent was evaporated off under reduced pressure
  12. customto give the crude product
  13. customwas purified by flash chromatography (Silica gel column, 100 g, DCM/EtOAc from 0% to 20EtOAc)
  14. customcrystallized from cyclohexane/DCM

Sources & evidence

ORD record
ord-0713fb0c0b4c480983380b0a2f56a4dc
Source dataset
uspto-grants-2016_04
Patent number
US09315489B2

Reaction notes

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