Boron tribromide → 2-Fluoro-4-[5-(methylsulfonyl)-2-pyridinyl]phenol

HRID 423575Notes

Reaction equation

HRID 423575 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C:16]2[CH:21]=[CH:20][C:19]([S:22]([CH3:25])(=[O:24])=[O:23])=[CH:18][N:17]=2)[CH:5]=[CH:6][C:7]=1[O:8]CC1C=CC=CC=1.B(Br)(Br)Br.C([O-])(O)=O.[Na+]>C(Cl)Cl>[F:1][C:2]1[CH:3]=[C:4]([C:16]2[CH:21]=[CH:20][C:19]([S:22]([CH3:25])(=[O:23])=[O:24])=[CH:18][N:17]=2)[CH:5]=[CH:6][C:7]=1[OH:8]

Participants

5

Reactant 3

HCID 25134Boron tribromideHCID 516892Sodium BicarbonateHCID 666731192-{3-Fluoro-4-[(phenylmethyl)oxy]phenyl}-5-(methylsulfonyl)pyridine

Product 1

HCID 1363884652-Fluoro-4-[5-(methylsulfonyl)-2-pyridinyl]phenolYield 93.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of 2-{3-fluoro-4-[(phenylmethyl)oxy]phenyl}-5-(methylsulfonyl)pyridine (0.166 g, 0.46 mmol) in CH2Cl2 (20 mL) was cooled to −78° C. BBr3 (0.18 mL, 1.86 mmol) was added dropwise. The reaction mixture was stirred at −78° C. to 0° C. for 2 h, poured into ice and aqueous NaHCO3 and extracted with EtOAc (60 mL×2). The combined organic extract was washed with brine, dried over Na2SO4, filtered, and the filtrate was concentrated to give a solid, which was triturated with hot hexanes containing 1% of CH2Cl2 and 1% of MeOH to give 0.115 g (93%) of 2-fluoro-4-[5-(methylsulfonyl)-2-pyridinyl]phenol as a yellow solid. 1H NMR (400 MHz, CD3OD): δ 9.05 (d, 1H, J=2.4 Hz), 8.29 (dd, 1H, Ja=8.4 Hz, Jb=2.4 Hz), 8.03 (d, 1H, J=8.3 Hz), 7.92 (dd, 1H, Ja=12.6 Hz, Jb=2.2 Hz), 7.85-7.75 (m, 1H), 7.03 (t, 1H, J=8.6 Hz), 3.21 (s, 3H); LRMS (ESI), m/z 268 (M+H).

Workup

  1. extractionextracted with EtOAc (60 mL×2)
  2. extractionThe combined organic extract
  3. washwas washed with brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationthe filtrate was concentrated
  7. customto give a solid, which
  8. customwas triturated with hot hexanes containing 1% of CH2Cl2 and 1% of MeOH

Sources & evidence

ORD record
ord-22418e8abe22452cafe53ee7300defac
Source dataset
uspto-grants-2012_01
Patent number
US08101634B2

Reaction notes

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