Boron tribromide → Ethyl 1-(6-(2-hydroxy-5-methylphenyl)pyridin-2-yl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxylate

HRID 1891221Notes

Reaction equation

HRID 1891221 reaction equation
C[O:2][C:3]1[CH:8]=[CH:7][C:6]([CH3:9])=[CH:5][C:4]=1[C:10]1[N:15]=[C:14]([N:16]2[C:20]([C:21]([F:24])([F:23])[F:22])=[C:19]([C:25]([O:27][CH2:28][CH3:29])=[O:26])[CH:18]=[N:17]2)[CH:13]=[CH:12][CH:11]=1.B(Br)(Br)Br>C(Cl)Cl>[OH:2][C:3]1[CH:8]=[CH:7][C:6]([CH3:9])=[CH:5][C:4]=1[C:10]1[N:15]=[C:14]([N:16]2[C:20]([C:21]([F:24])([F:23])[F:22])=[C:19]([C:25]([O:27][CH2:28][CH3:29])=[O:26])[CH:18]=[N:17]2)[CH:13]=[CH:12][CH:11]=1

Participants

4

Reactant 2

HCID 25134Boron tribromideHCID 67159458Ethyl 1-[6-(2-methoxy-5-methylphenyl)pyridin-2-yl]-5-(trifluoromethyl)-1H-pyrazole-4-carboxylate

Product 1

HCID 136017878Ethyl 1-(6-(2-hydroxy-5-methylphenyl)pyridin-2-yl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxylate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a cooled (0° C.) solution of the title compound from Example 12 Step A (1.58 g, 3.90 mmol) in DCM (20 mL) was added boron tribromide (11.7 mL, 1.0 M in DCM, 11.7 mmol). After 15 min, the reaction mixture was allowed to warm to ambient temperature. After an additional 2 h, the reaction mixture was cooled to 0° C., then was quenched by dropwise addition of sat. aq. NaHCO3 (gas evolution) and was extracted with DCM. The organic phase was separated and concentrated in vacuo. Purification by flash chromatography on silica gel (0 to 30% EtOAc in hexanes, then 30 to 100% EtOAc in hexanes) provided the title compound: LCMS m/z 392.6 [M+H]+; 1H NMR (500 MHz, CDCl3) δ 11.78 (s, 1H), 8.17 (s, 1H), 8.07-8.03 (m, 2H), 7.60 (d, J=1.5 Hz, 1H), 7.48 (dd, J=7.0, 1.5 Hz, 1H), 7.17 (dd, J=8.0, 2.0 Hz, 1H), 6.94 (d, J=8.0 Hz, 1H), 4.39 (q, J=7.0 Hz, 2H), 2.36 (s, 3H), 1.40 (t, J=7.0 Hz, 3H).

Workup

  1. waitAfter an additional 2 h
  2. temperaturethe reaction mixture was cooled to 0° C.
  3. customwas quenched by dropwise addition of sat. aq. NaHCO3 (gas evolution)
  4. extractionwas extracted with DCM
  5. customThe organic phase was separated
  6. concentrationconcentrated in vacuo
  7. customPurification by flash chromatography on silica gel (0 to 30% EtOAc in hexanes

Sources & evidence

ORD record
ord-599bad1a0f624f05bf5ad604a40c55ca
Source dataset
uspto-grants-2013_08
Patent number
US08507512B2

Reaction notes

Loading…