Boron tribromide → 3-({(2R)-4-[4-fluoro-2-(trifluoromethyl)phenyl]-2-methylpiperazin-1-yl}sulfonyl)phenol

HRID 1868128Notes

Reaction equation

HRID 1868128 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:13][CH2:12][N:11]([S:14]([C:17]3[CH:22]=[CH:21][CH:20]=[C:19]([O:23]C)[CH:18]=3)(=[O:16])=[O:15])[C@H:10]([CH3:25])[CH2:9]2)=[C:4]([C:26]([F:29])([F:28])[F:27])[CH:3]=1.CC(C)=O.C(=O)=O.B(Br)(Br)Br>ClCCl>[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:13][CH2:12][N:11]([S:14]([C:17]3[CH:18]=[C:19]([OH:23])[CH:20]=[CH:21][CH:22]=3)(=[O:16])=[O:15])[C@H:10]([CH3:25])[CH2:9]2)=[C:4]([C:26]([F:27])([F:28])[F:29])[CH:3]=1

Participants

5

Reactant 3

HCID 25134Boron tribromideHCID 18522661Acetone cardiceHCID 68551747(R)-4-(4-fluoro-2-(trifluoromethyl)phenyl)-1-(3-methoxyphenylsulfonyl)-2-methylpiperazine

Product 1

HCID 574183383-({(2R)-4-[4-fluoro-2-(trifluoromethyl)phenyl]-2-methylpiperazin-1-yl}sulfonyl)phenolYield 96%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A stirred solution of (R)-4-(4-fluoro-2-(trifluoromethyl)phenyl)-1-(3-methoxyphenylsulfonyl)-2-methylpiperazine (2.22 g, 5.13 mmol) in anhydrous dichloromethane (60 mL) was cooled down to −50° C. (acetone+dry ice bath). BBr3 (1M in CH2Cl2) was added dropwise via addition funnel while keeping the temperature between −50° C. and −55° C. Then the reaction mixture was stirred at −50° C. to −20° C. for 3 hours. Reaction was complete as determined by TLC. The reaction mixture was quenched with water and diluted with dichloromethane. pH was adjusted to 7 using saturated NaHCO3 (aqueous) and it was allowed to stir for 20 minutes. The layers were separated; the organic layer was dried over MgSO4 and concentrated. The reaction was repeated in 2.85 g scale. The combined crud products were purified via flash column chromatography to yield 3-({(2R)-4-[4-fluoro-2-(trifluoromethyl)phenyl]-2-methylpiperazin-1-yl}sulfonyl)phenol in 96% yield (4.07 g) as a white solid. HRMS: calcd for C18H18F4N2O3S+H+, 419.10470. found (ESI-FTMS, [M+H]1+), 419.104. HPLC Method 1: room temperature, 6.318 min, 100%, HPLC Method 2: room temperature, 7.220 min, 99.48%.

Workup

  1. customthe temperature between −50° C. and −55° C
  2. customReaction
  3. customThe reaction mixture was quenched with water
  4. additiondiluted with dichloromethane
  5. stirringto stir for 20 minutes
  6. customThe layers were separated
  7. dry with materialthe organic layer was dried over MgSO4
  8. concentrationconcentrated
  9. customThe combined crud products were purified via flash column chromatography

Sources & evidence

ORD record
ord-6b1e47a2805842c39c80d27c317fdaa0
Source dataset
uspto-grants-2009_12
Patent number
US07632838B2

Reaction notes

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