1,2-Dimethoxyethane → Ethyl [5-benzyloxy-4'-(trifluoromethyl)biphenyl-3-yl]acetate

HRID 888650Notes

Reaction equation

[CH2:1]([O:3][C:4](=[O:28])[CH2:5][C:6]1[CH:11]=[C:10](OS(C(F)(F)F)(=O)=O)[CH:9]=[C:8]([O:20][CH2:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[CH:7]=1)[CH3:2].[F:29][C:30]([F:41])([F:40])[C:31]1[CH:36]=[CH:35][C:34](B(O)O)=[CH:33][CH:32]=1.COCCOC.C([O-])([O-])=O.[Na+].[Na+]>CCOC(C)=O>[CH2:1]([O:3][C:4](=[O:28])[CH2:5][C:6]1[CH:11]=[C:10]([C:34]2[CH:35]=[CH:36][C:31]([C:30]([F:41])([F:40])[F:29])=[CH:32][CH:33]=2)[CH:9]=[C:8]([O:20][CH2:21][C:22]2[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=2)[CH:7]=1)[CH3:2]

Participants

Conditions

Temperature: 95 °C

Procedure

A mixture of (3-benzyloxy-5-trifluoromethanesulfonyloxy-phenyl)-acetic acid ethyl ester (108 g, 0.26 mol), 4-(trifluoromethyl)phenylboronic acid (55.6 g, 0.29 mol), 1,2-dimethoxyethane (1.1 L) and aqueous Na2CO3 (2 M, 129 mL, 0.26 mol) was mechanically stirred while purging N2 at room temperature for 10 min. To this system was added Pd(Ph3)4 (480 mg, 0.42 mmol) and heated to reflux (95° C.) for 2.5 h. The red-brown mixture was diluted with EtOAc (0.5 L) and washed with saturated aqueous NaHCO3 solution (3×200 mL) and brine (2×200 mL). The organic fraction was dried (Na2SO4) and concentrated in vacuo. The crude mixture was purified by ISCO column chromatography to obtain (5-benzyloxy-4′-trifluoromethyl-biphenyl-3-yl)-acetic acid ethyl ester (107 g, 100%).

Workup

customwhile purging N2 at room temperature for 10 min
temperatureheated
washwashed with saturated aqueous NaHCO3 solution (3×200 mL) and brine (2×200 mL)
dry with materialThe organic fraction was dried (Na2SO4)
concentrationconcentrated in vacuo
customThe crude mixture was purified by ISCO column chromatography

Sources & evidence

ORD record: ord-a8b352b1186e43a5b0c7be3109a891ea
Source dataset: uspto-grants-2012_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08247610B2

Reaction notes

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