2-(Bromomethyl)-1,3-difluorobenzene → HCID 68709545, compound

HRID 2113693Notes

Reaction equation

[OH:1][N:2]1[CH:6]=[CH:5][CH:4]=[N:3]1.[F:7][C:8]1[CH:15]=[CH:14][CH:13]=[C:12]([F:16])[C:9]=1[CH2:10]Br>C(Cl)(Cl)Cl>[F:7][C:8]1[CH:15]=[CH:14][CH:13]=[C:12]([F:16])[C:9]=1[CH2:10][N:3]1[CH2:4][CH:5]=[CH:6][N:2]1[OH:1]

Participants

Conditions

Temperature: 80 °C

Procedure

1-Hydroxypyrazole (49.3 mg, 0.59 mmol, 1.0 eq) was mixed with 165.8 mg (0.80 mmol, 1.36 eq) of 2,6-difluorobenzyl bromide in ˜1-2 mL of anhydrous CHCl3 under argon. The mixture was heated at 80° C. for 18 h under inert atmosphere in a sealed flask without condenser. The residue was partitioned between 37 weight percent aqueous HCl and toluene. The aqueous layer was collected and the toluene fraction extracted again with 37 weight percent aqueous HCl. The combined aqueous HCL fractions were neutralized with 5N aqueous NaOH to pH˜11-12 and then back-extracted with 3×30 mL of CHCl3. The organic layers were combined, washed with brine, dried over Na2SO4 and concentrated under reduced pressure to yield 86.3 mg (70.1% yield) of 2-(2,6-difluorobenzyl)-1-hydroxy-1H-pyrazole as a tan brown solid. 1H NMR (CDCl3 300 MHz) δ 7.37 (m, 1H), 7.18 (d, 1H), 6.95 (t, 2H), 6.85 (d, 1H), 6.11 (t, 1H), 5.43 (s, 2.00 H). LC/MS (ES) M+1=211.2

Workup

customThe residue was partitioned between 37 weight percent aqueous HCl and toluene
customThe aqueous layer was collected
extractionthe toluene fraction extracted again with 37 weight percent aqueous HCl
extractionback-extracted with 3×30 mL of CHCl3
washwashed with brine
dry with materialdried over Na2SO4
concentrationconcentrated under reduced pressure

Sources & evidence

ORD record: ord-70dc44f1f15e433f90ab7dccac050fd8
Source dataset: uspto-grants-2008_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07432266B2

Reaction notes

Loading…