Potassium Phosphate, Tribasic → 4'-Chloro-3-methoxy-biphenyl-4-carboxylic acid methyl ester

HRID 1430187Notes

Reaction equation

Br[C:2]1[CH:11]=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[C:4]([O:12][CH3:13])[CH:3]=1.[Cl:14][C:15]1[CH:20]=[CH:19][C:18](B(O)O)=[CH:17][CH:16]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.CO.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[CH3:9][O:8][C:6]([C:5]1[CH:10]=[CH:11][C:2]([C:18]2[CH:19]=[CH:20][C:15]([Cl:14])=[CH:16][CH:17]=2)=[CH:3][C:4]=1[O:12][CH3:13])=[O:7]

Participants

Conditions

Temperature: 80 °C

Procedure

To a degassed solution of methyl 4-bromo-2-methoxybenzoate (0.70 g, 2.86 mmol) in 1,4-dioxane (10 mL) and MeOH (2.5 mL) at room temperature under nitrogen blanketing is added 4-chlorophenyl boronic acid (0.536 g, 3.43 mmol), Pd(dppf)Cl2 (0.233 g, 0.286 mmol) and K3PO4 (0.728 g, 3.43 mmol). The resulting suspension is heated to 80° C. and stirred for 3 hours after which the reaction is cooled to room temperature and filtered through Celite™. The collected solids are washed with additional MeOH and the filtrate concentrated under reduced pressure. The crude material is purified over silica (hexanes:EtOAc gradient 6:1 to 4:1) to afford 0.614 g (78% yield) of the desired product as orange crystals. 1H NMR (400 MHz, CDCl3) δ ppm 7.89 (1H, d, J=8.0 Hz), 7.52-7.56 (2H, m), 7.44 (2H, d, J=8.7 Hz), 7.17 (1H, d, J=8.0 Hz), 7.12 (1H, d, J=1.6 Hz), 3.99 (3H, s), 3.92 (3H, s). HPLC-MS: m/z 277 [M+H]+.

Workup

temperatureis cooled to room temperature
filtrationfiltered through Celite™
washThe collected solids are washed with additional MeOH
concentrationthe filtrate concentrated under reduced pressure
customThe crude material is purified over silica (hexanes:EtOAc gradient 6:1 to 4:1)

Sources & evidence

ORD record: ord-cd639a521cbb4c27b3e83b8812b02564
Source dataset: uspto-grants-2015_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08940773B2

Reaction notes

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