1,2-Dimethoxyethane → 3'-Chloro-2-fluoro-6-methoxy-3-(4-nitro-benzyl)-biphenyl

HRID 1632029Notes

Reaction equation

HRID 1632029 reaction equation
Br[CH2:2][C:3]1[C:4]([F:18])=[C:5]([C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([Cl:17])[CH:12]=2)[C:6]([O:9][CH3:10])=[CH:7][CH:8]=1.[N+:19]([C:22]1[CH:27]=[CH:26][C:25](B(O)O)=[CH:24][CH:23]=1)([O-:21])=[O:20].P([O-])([O-])([O-])=O.[K+].[K+].[K+].C(COC)OC>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.C(O)C>[Cl:17][C:13]1[CH:12]=[C:11]([C:5]2[C:6]([O:9][CH3:10])=[CH:7][CH:8]=[C:3]([CH2:2][C:25]3[CH:26]=[CH:27][C:22]([N+:19]([O-:21])=[O:20])=[CH:23][CH:24]=3)[C:4]=2[F:18])[CH:16]=[CH:15][CH:14]=1

Participants

7

Reactant 4

HCID 80711,2-DimethoxyethaneHCID 62657Potassium Phosphate, TribasicHCID 27735524-Nitrophenylboronic acidHCID 577037013-Bromomethyl-3'-chloro-2-fluoro-6-methoxy-biphenyl

Product 1

HCID 580201863'-Chloro-2-fluoro-6-methoxy-3-(4-nitro-benzyl)-biphenylYield 76%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolvent

Conditions

Temperature
60 °C

Procedure

In a 40 mL vial equipped with a stir bar was placed 3-bromomethyl-3′-chloro-2-fluoro-6-methoxy-biphenyl (I-33, 400 mg, 1.21 mmol), 4-nitrophenylboronic acid (420 mg, 1.45 mmol), potassium phosphate (tribasic) (514 mg, 2.42 mmol), dimethoxyethane (3.5 mL) and 50% aqueous ethanol (3.5 mL). After degassing with nitrogen for 15 minutes, tetrakis(triphenylphosphine)palladium(0) (140 mg, 0.121 mmol) was added. The mixture was heated to 60° C. for 18 hours and then the palladium catalyst was removed by filtering through Celite. To the filtrate were added water (50 mL) and a saturated ammonium chloride solution (50 mL). After extracting with ethyl acetate (3×50 mL), the organic portions were combined, washed with brine (75 mL), dried (MgSO4) and concentrated. The crude material was purified by silica gel chromatography utilizing 20% ethyl acetate/hexanes as eluent to produce 342 mg (76%) of 3′-chloro-2-fluoro-6-methoxy-3-(4-nitro-benzyl)-biphenyl (I-34) as a yellow solid. MS (APCI−): 370.1 (M−1).

Workup

  1. customIn a 40 mL vial equipped with a stir bar
  2. customAfter degassing with nitrogen for 15 minutes
  3. customthe palladium catalyst was removed
  4. filtrationby filtering through Celite
  5. additionTo the filtrate were added water (50 mL)
  6. extractionAfter extracting with ethyl acetate (3×50 mL)
  7. washwashed with brine (75 mL)
  8. dry with materialdried (MgSO4)
  9. concentrationconcentrated
  10. customThe crude material was purified by silica gel chromatography

Sources & evidence

ORD record
ord-8468ac35d8634dceb4a5a52c0da83393
Source dataset
uspto-grants-2014_07
Patent number
US08791267B2

Reaction notes

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