Boron tribromide → 3-((4-(4-(2,2,2-Trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl)phenyl)-1-piperazinyl)sulfonyl)phenol

HRID 1972485Notes

Reaction equation

HRID 1972485 reaction equation
[F:1][C:2]([F:33])([F:32])[C:3]([C:9]1[CH:14]=[CH:13][C:12]([N:15]2[CH2:20][CH2:19][N:18]([S:21]([C:24]3[CH:29]=[CH:28][CH:27]=[C:26]([O:30]C)[CH:25]=3)(=[O:23])=[O:22])[CH2:17][CH2:16]2)=[CH:11][CH:10]=1)([OH:8])[C:4]([F:7])([F:6])[F:5].B(Br)(Br)Br>C(Cl)Cl>[F:33][C:2]([F:1])([F:32])[C:3]([C:9]1[CH:14]=[CH:13][C:12]([N:15]2[CH2:20][CH2:19][N:18]([S:21]([C:24]3[CH:25]=[C:26]([OH:30])[CH:27]=[CH:28][CH:29]=3)(=[O:23])=[O:22])[CH2:17][CH2:16]2)=[CH:11][CH:10]=1)([OH:8])[C:4]([F:7])([F:6])[F:5]

Participants

4

Reactant 2

HCID 25134Boron tribromideHCID 866703641,1,1,3,3,3-Hexafluoro-2-(4-(4-((3-methoxyphenyl)sulfonyl)-1-piperazinyl)phenyl)-2-propanol

Product 1

HCID 569324713-((4-(4-(2,2,2-Trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl)phenyl)-1-piperazinyl)sulfonyl)phenol

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A 25 ml, round-bottomed flask was charged with 1,1,1,3,3,3-hexafluoro-2-(4-(4-((3-methoxyphenyl)sulfonyl)-1-piperazinyl)phenyl)-2-propanol (80 mg, 0.16 mmol) and CH2Cl2 (5 mL). BBr3 (1M in CH2Cl2, 0.48 mL, 0.48 mmol) was added at room temperature. The reaction was stirred at room temperature for 1 h. The mixture was quenched with MeOH (20 mL), concentrated onto silica gel and purified via column chromatography (12 g silica gel, 0 to 10% MeOH in CH2Cl2) to give 3-((4-(4-(2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl)phenyl)-1-piperazinyl)sulfonyl)phenol. 1H NMR (400 MHz, CD3OD) δ=7.57 (d, J=9.0 Hz, 2H), 7.44 (t, J=8.0 Hz, 1H), 7.25 (d, J=7.4 Hz, 1H), 7.18 (s, 1H), 7.10-7.06 (m, 1H), 7.04 (d, J=9.2 Hz, 2H), 3.37-3.33 (m, 4H), 3.21-3.07 (m, 4H). m/z (ESI, +ve ion) 485.1 (M+H)+. GK-GKRP IC50 (Binding)=0.949 μM; GK-GKRP EC50 (LC MS/MS-2)=0.74 μM.

Workup

  1. customThe mixture was quenched with MeOH (20 mL)
  2. concentrationconcentrated onto silica gel
  3. custompurified via column chromatography (12 g silica gel, 0 to 10% MeOH in CH2Cl2)

Sources & evidence

ORD record
ord-172afd27be594b9aa5afb580f6689b1d
Source dataset
uspto-grants-2013_04
Patent number
US08431563B2

Reaction notes

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