Toluene → 5'-Bromo-2',6-difluoro-[1,1'-biphenyl]-2-ol

HRID 1400772Notes

Reaction equation

[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([OH:8])[C:3]=1B(O)O.C([O-])([O-])=O.[Na+].[Na+].C1(C)C=CC=CC=1.[Br:25][C:26]1[CH:31]=[CH:30][C:29]([F:32])=[C:28](I)[CH:27]=1>CO.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Br:25][C:26]1[CH:27]=[CH:28][C:29]([F:32])=[C:30]([C:3]2[C:4]([OH:8])=[CH:5][CH:6]=[CH:7][C:2]=2[F:1])[CH:31]=1

Participants

Conditions

Temperature: 105 °C

Procedure

(2-Fluoro-6-hydroxyphenyl)boronic acid (50 mg, 0.321 mmol, 1.0 equiv), Pd(PPh3)4 (37.1 mg, 0.032 mmol, 0.1 equiv) and aqueous Na2CO3 (2 M, 401 μl, 0.802 mmol, 2.5 equiv) were mixed with toluene (2 mL) in a sealed microwave tube. 4-Bromo-1-fluoro-2-iodobenzene (96 mg, 0.321 mmol, 1.0 equiv) in MeOH (1.00 mL) was added to the above mixture. The resulted mixture was heated at 105° C. overnight. TLC showed the starting material disappeared and a new spot was produced. The reaction was allowed to cool to ambient temperature and then loaded on 12 g ISCO column and purified by 30% EtOAc/hexane to afford 5′-bromo-2′,6-difluoro-[1,1′-biphenyl]-2-ol (81 mg, 89%). 1H NMR (400 MHz, CHLOROFORM-d) δ 7.54 (dd, J=6.3, 2.5 Hz, 1H), 7.48 (ddd, J=8.7, 4.5, 2.6 Hz, 1H), 7.21 (td, J=8.2, 6.7 Hz, 1H), 7.07 (t, J=8.9 Hz, 1H), 6.81 (d, J=8.3 Hz, 1H), 6.71 (t, J=8.8 Hz, 1H). LCMS (M+1)=286.1.

Workup

customa new spot was produced
temperatureto cool to ambient temperature
custompurified by 30% EtOAc/hexane

Sources & evidence

ORD record: ord-e738820b20ae42f688c3f0b5e687080d
Source dataset: uspto-grants-2014_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08906929B2

Reaction notes

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