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

HRID 1400778Notes

Reaction equation

[Cl: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[Cl:1])[CH:31]=1

Participants

Conditions

Temperature: 105 °C

Procedure

(2-Chloro-6-hydroxyphenyl)boronic acid (250 mg, 1.450 mmol, 1.0 equiv), Pd(PPh3)4 (168 mg, 0.145 mmol, 0.1 equiv) and aqueous Na2CO3 (2 M, 1.8 mL, 3.63 mmol, 2.5 equiv) were mixed with toluene (3 mL) in a sealed microwave tube. 4-Bromo-1-fluoro-2-iodobenzene (436 mg, 1.450 mmol) in MeOH (1.50 mL) was added to the above mixture. The mixture was heated at 105° C. overnight. Then, the reaction mixture was loaded on 12 g column and purified using 30% EtOAc/Hex to afford 5′-bromo-6-chloro-2′-fluoro-[1,1′-biphenyl]-2-ol (400 mg, 91% yield). 1H NMR (400 MHz, CDCl3) δ 7.57 (ddd, J=8.8, 4.5, 2.5 Hz, 1H), 7.47 (dd, J=6.3, 2.5 Hz, 1H), 7.24 (t, J=8.2 Hz, 1H), 7.17-7.06 (m, 2H), 6.90 (d, J=8.0 Hz, 1H). LCMS (M+1)=302.9.

Workup

custompurified

Sources & evidence

ORD record: ord-19daac34860a47089e1a48afd8595752
Source dataset: uspto-grants-2014_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08906929B2

Reaction notes

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