Hydrochloric Acid → [2-Fluoro-4-(methylsulfanyl)phenyl]boronic acid

HRID 423646Notes

Reaction equation

HRID 423646 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([S:8][CH3:9])=[CH:4][C:3]=1[F:10].[Li]CCCC.[B:16](OC)([O:19]C)[O:17]C.Cl>C1COCC1.CCOCC>[F:10][C:3]1[CH:4]=[C:5]([S:8][CH3:9])[CH:6]=[CH:7][C:2]=1[B:16]([OH:19])[OH:17]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 8470Trimethyl borateHCID 253072224-Bromo-3-fluorothioanisoleHCID 178418339Butyllithium

Product 1

HCID 44717667[2-Fluoro-4-(methylsulfanyl)phenyl]boronic acidYield 16.3%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent

Procedure

A stirred solution of 1-bromo-2-fluoro-4-(methylthio)benzene (180 g, 814 mmol) at −78° C. in THF (500 mL) was treated with n-BuLi (358 mL, 2.5M in hexanes, 895 mmol) over 1.5 h. After 15 min at −78° C., B(OMe)3 (254 g, 244 mol) was added over 1.5 h, and the reaction mixture was slowly warmed to ambient temperature. 10% Aqueous HCl (100 mL) was added and the mixture was stirred for 5 min. Et2O (500 mL) was added and the organic layer was separated and washed with 2M NaOH (300 mL). The aqueous phase was rinsed one more time with Et2O. The aqueous phase was then acidified with 10% aqueous HCl to pH ˜4 and the resulting solid was collected to give [2-fluoro-4-(methylthio)phenyl]boronic acid (24.7 g). 1H NMR (400 MHz, CDCl3): δ 7.70 (t, 1H, J=7.6 Hz), 7.03 (dd, 1H, Ja=8.1 Hz, Jb=1.6 Hz), 6.88 (dd, 1H, Ja=11.7 Hz, Jb=1.6 Hz), 2.49 (s, 3H).

Workup

  1. customthe organic layer was separated
  2. washwashed with 2M NaOH (300 mL)
  3. washThe aqueous phase was rinsed one more time with Et2O
  4. customthe resulting solid was collected

Sources & evidence

ORD record
ord-8ad254302f2a42ad8c63fcc0dcbe4d3b
Source dataset
uspto-grants-2012_01
Patent number
US08101634B2

Reaction notes

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