Sodium Carbonate → Methyl 2'-fluoro-4'-methoxy-2-methylbiphenyl-4-carboxylate

HRID 604686Notes

Reaction equation

HRID 604686 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([O:8][CH3:9])=[CH:4][C:3]=1[F:10].[CH3:11][C:12]1[CH:13]=[C:14]([CH:19]=[CH:20][C:21]=1B1OC(C)(C)C(C)(C)O1)[C:15]([O:17][CH3:18])=[O:16].C([O-])([O-])=O.[Na+].[Na+].C(Cl)Cl.CCCCCC>O.CCO.C1(C)C=CC=CC=1.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[F:10][C:3]1[CH:4]=[C:5]([O:8][CH3:9])[CH:6]=[CH:7][C:2]=1[C:21]1[CH:20]=[CH:19][C:14]([C:15]([O:17][CH3:18])=[O:16])=[CH:13][C:12]=1[CH3:11]

Participants

7

Reactant 4

HCID 10340Sodium CarbonateHCID 37184441-Bromo-2-fluoro-4-methoxybenzeneHCID 110870242-Methyl-4-methoxycarbonylphenylboronic acid, pinacol ester2×HCID 21226440Methylenechloride Hexane

Product 1

HCID 57704800Methyl 2'-fluoro-4'-methoxy-2-methylbiphenyl-4-carboxylate

Reagents, catalysts & solvents 2

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 86587398Ethanol toluene waterSolvent

Procedure

A mixture of 4-bromo-3-fluoro anisole (500 mg, 2.44 mmol), methyl 3-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoate (INTERMEDIATE 37, 875 mg, 3.17 mmol), tetrakis(triphenylphosphine) palladium (282 mg, 5% mol) and Na2CO3 (569 mg, 5.37 mmol) in 20 mL of water/EtOH/toluene (1:2:4) was heated at reflux for 4 h. TLC (CH2Cl2/hexane (1:1)) showed that the reaction was complete. The solvents were removed. Water (10 mL) was added. The organic was extracted with CH2Cl2 (3×10 mL). The combined CH2Cl2 layers were washed with brine and then dried (Na2SO4). The title compound was obtained after flash chromatography using CH2Cl2/hexanes (6:4) as the eluent. 1H NMR (500 MHz, CDCl3): δ 7.98 (s, 1H), 7.92 (dd, J=8.0, 1.5 Hz, 1H), 7.29 (d, J=8.0 Hz, 1H), 7.16 (t, J=8.5 Hz, 1H), 6.80 (dd, J=8.5, 2.5 Hz, 1H), 6.77 (dd, J=11.5, 2.5 Hz, 1H), 3.95 (s, 3H), 3.88 (s, 3H), 2.28 (s, 3H).

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 4 h
  3. customThe solvents were removed
  4. additionWater (10 mL) was added
  5. extractionThe organic was extracted with CH2Cl2 (3×10 mL)
  6. washThe combined CH2Cl2 layers were washed with brine
  7. dry with materialdried (Na2SO4)

Sources & evidence

ORD record
ord-99faff6030fc460896669e2cda2d8647
Source dataset
uspto-grants-2011_03
Patent number
US07910592B2

Reaction notes

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