Boron tribromide → 3-Chloro-4-[5-(4-ethylbicyclo[2.2.2]oct-1-yl)-4-methyl-4h-1,2,4-triazol-3-yl]phenol

HRID 22851Notes

Reaction equation

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

Participants

Conditions

Temperature: 0 °C

Procedure

Triazole 9-D (30 mg, 0.08 mmol) was dissolved in 0.5 mL of dry methylene chloride, placed under an inert atmosphere, and cooled to 0° C. To this solution was added BBr3 (1 M in CH2Cl2, 0.25 mL, 0.25 mmol) and the cooling bath was immediately removed. The reaction was stirred for 2 h then diluted with 20 mL of methylene chloride and washed with 1 N aqueous NaOH and brine. The residue was chromatographed by reverse-phase HPLC, eluting with a gradient of 0 to 100% acetonitrile in water. The product, 3-chloro-4-[5-(4-ethylbicyclo[2.2.2]oct-1-yl)4-methyl-4 H-1,2,4-triazol-3-yl]phenol (9-E), was isolated as a white powder. MS (ESI+)=346.2 (M+1); 1H NMR (500 MHz, CDCl3): δ 0.85 (3H, t, J=7.5 Hz), 1.25 (2H, q, J=7.5 Hz), 1.55 (6H, m), 2.13 (6H, m), 3.58 (3H, s), 6.68 (1H, dd, J=8.4 Hz, J=2.6 Hz), 6.91 (1H, d, J=2.6 Hz), 7.10 (1H, d, J=8.4 Hz).

Workup

customthe cooling bath was immediately removed
additionthen diluted with 20 mL of methylene chloride
washwashed with 1 N aqueous NaOH and brine
customThe residue was chromatographed by reverse-phase HPLC
washeluting with a gradient of 0 to 100% acetonitrile in water

Sources & evidence

ORD record: ord-6873e92a150b4d99b3a5a7eb43412061
Source dataset: uspto-grants-2005_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06849636B2

Reaction notes

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