Sodium Carbonate → (2-Cyclopropyl-4'-fluoro-6-propoxybiphenyl-4-yl)methanol

HRID 531011Notes

Reaction equation

HRID 531011 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:13](OS(C(F)(F)F)(=O)=O)=[CH:12][C:11]([C:22]([O:24]CC)=O)=[CH:10][C:9]=2[O:27][CH2:28][CH2:29][CH3:30])=[CH:4][CH:3]=1.[CH:31]1(B(O)O)[CH2:33][CH2:32]1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC)=CC=CC=2OC)CCCCC1.C(=O)([O-])[O-].[Na+].[Na+]>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1(C)C=CC=CC=1>[CH:31]1([C:13]2[CH:12]=[C:11]([CH2:22][OH:24])[CH:10]=[C:9]([O:27][CH2:28][CH2:29][CH3:30])[C:8]=2[C:5]2[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=2)[CH2:33][CH2:32]1

Participants

7

Reactant 4

HCID 10340Sodium CarbonateHCID 2760897Cyclopropylboronic acidHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 117992413Ethyl 4'-fluoro-2-propoxy-6-(((trifluoromethyl)sulfonyl)oxy)biphenyl-4-carboxylate

Product 1

HCID 117992501(2-Cyclopropyl-4'-fluoro-6-propoxybiphenyl-4-yl)methanolYield 100.2%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Procedure

Tris(dibenzylideneacetone)dipalladium(0) (6.65 g) was added to a mixture of ethyl 4′-fluoro-2-propoxy-6-(((trifluoromethyl)sulfonyl)oxy)biphenyl-4-carboxylate (44.6 g), cyclopropylboronic acid (22.3 g), dicyclohexyl(2′,6′-dimethoxybiphenyl-2-yl)phosphine (6.38 g), a 2 M aqueous sodium carbonate solution (156 mL), and toluene (250 mL), and the resultant mixture was stirred at 100° C. for 4 hours in an argon atmosphere. The reaction mixture was allowed to cool to room temperature, followed by extraction with ethyl acetate. The obtained organic layer was washed with saturated saline and dried over anhydrous magnesium sulfate, and then, the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel chromatography (hexane/ethyl acetate). A THF (150 mL) solution of the obtained purified product was added to a THF (150 mL) suspension of lithium aluminum hydride (3.50 g) under ice cooling in a nitrogen atmosphere. After stirring at the same temperature as above for 30 minutes, water (3.5 mL) and a 15% aqueous sodium hydroxide solution (3.5 mL) were added thereto, and the mixture was stirred for 5 minutes. Then, water (10.5 mL) was further added thereto, and the mixture was stirred for 30 minutes. The reaction mixture was filtered, and the filtrate was concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (hexane/ethyl acetate) to obtain the title compound (29.8 g).

Workup

  1. extractionfollowed by extraction with ethyl acetate
  2. washThe obtained organic layer was washed with saturated saline
  3. dry with materialdried over anhydrous magnesium sulfate
  4. distillationthe solvent was distilled off under reduced pressure
  5. customThe obtained residue was purified by silica gel chromatography (hexane/ethyl acetate)
  6. customA THF (150 mL) solution of the obtained purified product
  7. additionwas added to a THF (150 mL) suspension of lithium aluminum hydride (3.50 g) under ice cooling in a nitrogen atmosphere
  8. additiona 15% aqueous sodium hydroxide solution (3.5 mL) were added
  9. stirringthe mixture was stirred for 5 minutes
  10. additionThen, water (10.5 mL) was further added
  11. stirringthe mixture was stirred for 30 minutes
  12. filtrationThe reaction mixture was filtered
  13. concentrationthe filtrate was concentrated under reduced pressure
  14. customThe obtained residue was purified by silica gel column chromatography (hexane/ethyl acetate)

Sources & evidence

ORD record
ord-dc763c7d38374b568eeb7c50c3d06c78
Source dataset
uspto-grants-2016_05
Patent number
US09353108B2

Reaction notes

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