Potassium Carbonate → Methyl 2'-ethyl-2-(methoxymethyl)-[1,1'-biphenyl]-4-carboxylate

HRID 2410481Notes

Reaction equation

HRID 2410481 reaction equation
Br[C:2]1[CH:11]=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[CH:4][C:3]=1[CH2:12][O:13][CH3:14].F[C:16]1[C:17](C)=[C:18]([C:22]2C=CC(C(O)=O)=C[C:23]=2COC)[CH:19]=[CH:20][CH:21]=1.C(C1C=CC=CC=1B(O)O)C.C(=O)([O-])[O-].[K+].[K+]>C1(C)C=CC=CC=1.O.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>[CH2:22]([C:18]1[CH:19]=[CH:20][CH:21]=[CH:16][C:17]=1[C:2]1[CH:11]=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[CH:4][C:3]=1[CH2:12][O:13][CH3:14])[CH3:23]

Participants

8

Reactant 4

HCID 11430Potassium CarbonateHCID 41008622-Ethylphenylboronic Acid (contains varying amounts of Anhydride)HCID 580663983'-Fluoro-2-(methoxymethyl)-2'-methylbiphenyl-4-carboxylic acidHCID 58554220Methyl 4-bromo-3-(methoxymethyl)benzoate

Product 1

HCID 58554174Methyl 2'-ethyl-2-(methoxymethyl)-[1,1'-biphenyl]-4-carboxylateYield 83%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of methyl 4-bromo-3-(methoxymethyl)benzoate (Intermediate 1 Step 2, 12.0 g, 46.3 mmol) in toluene (150 mL) and water (35 mL) under N2, was added 2-ethylbenzene boronic acid (9.02 g, 60.1 mmol) followed by potassium carbonate (19 g, 139 mmol) and Pd(PPh3)4 (2.67 g, 2.31 mmol). The reaction mixture was degassed with N2 and heated at 100° C. for 12 hours. The reaction mixture was diluted with EtOAc. The organic layer was washed with a saturated aqueous solution of sodium bicarbonate (100 mL), water (2×100 mL) and brine (100 mL). It was then dried over sodium sulphate and concentrated under reduced pressure. The residue was purified by chromatography (silica gel, pet ether/EtOAc) to afford the title compound as a pale yellow liquid (12.0 g, 83%). 1H NMR (CDCl3, 400 MHz) δ 8.25 (1H, s), 8.00 (1H, d), 7.35 (2H, m), 7.25 (2H, m), 7.08 (1H, d), 4.12-4.21 (2H, m), 3.94 (3H, s), 3.29 (3H, s), 2.28-2.43 (2H, m), 1.03 (3H, t).

Workup

  1. customThe reaction mixture was degassed with N2
  2. additionThe reaction mixture was diluted with EtOAc
  3. washThe organic layer was washed with a saturated aqueous solution of sodium bicarbonate (100 mL), water (2×100 mL) and brine (100 mL)
  4. dry with materialIt was then dried over sodium sulphate
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by chromatography (silica gel, pet ether/EtOAc)

Sources & evidence

ORD record
ord-d3f34a66e203473cbe81b7be6f14f4bd
Source dataset
uspto-grants-2014_08
Patent number
US08815919B2

Reaction notes

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