Toluene → (3'-Chloro-2-fluoro-6-methoxy-biphenyl-3-yl)-methanol

HRID 1632027Notes

Reaction equation

HRID 1632027 reaction equation
Br[C:2]1[C:3]([F:12])=[C:4]([CH2:10][OH:11])[CH:5]=[CH:6][C:7]=1[O:8][CH3:9].[Cl:13][C:14]1[CH:15]=[C:16](B(O)O)[CH:17]=[CH:18][CH:19]=1.C([O-])([O-])=O.[Na+].[Na+].C1(C)C=CC=CC=1>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.CCO>[Cl:13][C:14]1[CH:19]=[C:18]([C:2]2[C:7]([O:8][CH3:9])=[CH:6][CH:5]=[C:4]([CH2:10][OH:11])[C:3]=2[F:12])[CH:17]=[CH:16][CH:15]=1

Participants

7

Reactant 4

HCID 1140TolueneHCID 10340Sodium CarbonateHCID 2734323(3-Chlorophenyl)boronic acidHCID 57703782(3-Bromo-2-fluoro-4-methoxyphenyl)methanol

Product 1

HCID 57703788(3'-Chloro-2-fluoro-6-methoxy-biphenyl-3-yl)-methanolYield 74.1%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolvent

Conditions

Temperature
80 °C

Procedure

Into a 100 mL round bottom flask was added (3-bromo-2-fluoro-4-methoxy-phenyl)-methanol (I-31, 1.04 g, 4.0 mmol), 3-chlorophenylboronic acid (0.76 g, 4.8 mmol), Pd(PPh3)4 (0.45 g, 0.41 mmol), Na2CO3 (6 mL, 2M aq), toluene, (32 mL), and EtOH (11 mL). The reaction was degassed with N2, then stirred at 80° C. for 24 hours. Water was added and the product was extracted with ethyl acetate. The combined organics were concentrated and filtered through a SiO2 plug eluting with 50% ethyl acetate/hexanes. The solid was triturated with ether and filtered. The filtrate was concentrated and triturated with ether and filtered. The filter cakes were combined and purified by flash column chromatography eluting with 20% acetone/hexanes to give (3′-chloro-2-fluoro-6-methoxy-biphenyl-3-yl)-methanol (I-32, 0.79 g, 67%) as a white solid.

Workup

  1. customThe reaction was degassed with N2
  2. additionWater was added
  3. extractionthe product was extracted with ethyl acetate
  4. concentrationThe combined organics were concentrated
  5. filtrationfiltered through a SiO2 plug
  6. washeluting with 50% ethyl acetate/hexanes
  7. customThe solid was triturated with ether
  8. filtrationfiltered
  9. concentrationThe filtrate was concentrated
  10. customtriturated with ether
  11. filtrationfiltered
  12. custompurified by flash column chromatography
  13. washeluting with 20% acetone/hexanes

Sources & evidence

ORD record
ord-005c295a104b456bba38f83387c612e3
Source dataset
uspto-grants-2014_07
Patent number
US08791267B2

Reaction notes

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