Sodium Carbonate → (2-Cyclopropyl-4'-fluoro-5-isopropoxybiphenyl-4-yl)methanol

HRID 531002Notes

Reaction equation

HRID 531002 reaction equation
Br[C:2]1[CH:7]=[C:6]([C:8](OC)=[O:9])[C:5]([O:12][CH:13]([CH3:15])[CH3:14])=[CH:4][C:3]=1[C:16]1[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=1.[CH:23]1(B(O)O)[CH2:25][CH2:24]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:23]1([C:2]2[CH:7]=[C:6]([CH2:8][OH:9])[C:5]([O:12][CH:13]([CH3:14])[CH3:15])=[CH:4][C:3]=2[C:16]2[CH:17]=[CH:18][C:19]([F:22])=[CH:20][CH:21]=2)[CH2:25][CH2:24]1

Participants

7

Reactant 4

HCID 10340Sodium CarbonateHCID 2760897Cyclopropylboronic acidHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 117992274Methyl 2-bromo-4'-fluoro-5-isopropoxy-[1,1'-biphenyl]-4-carboxylate

Product 1

HCID 117992161(2-Cyclopropyl-4'-fluoro-5-isopropoxybiphenyl-4-yl)methanolYield 93.4%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Procedure

A mixture of methyl 2-bromo-4′-fluoro-5-isopropoxybiphenyl-4-carboxylate (7.53 g), cyclopropylboronic acid (4.40 g), dicyclohexyl(2′,6′-dimethoxybiphenyl-2-yl)phosphine (1.26 g), a 2 M aqueous sodium carbonate solution (30.8 mL), tris(dibenzylideneacetone)dipalladium(0) (1.31 g), and toluene (150 mL) was stirred overnight at 100° C. in an argon atmosphere. The reaction mixture was allowed to cool to room temperature. Then, the organic layer was separated, washed with saturated saline, and passed through a short silica gel (NH) column, and the solvent was distilled off under reduced pressure. A THF (50 mL) solution of the obtained residue was added to a THF (50 mL) suspension of lithium aluminum hydride (2.00 g) under ice cooling in a nitrogen atmosphere. After stirring at the same temperature as above for 30 minutes, water (2 mL) and a 15% aqueous sodium hydroxide solution (2 mL) were added thereto, and the mixture was stirred for 5 minutes. Water (6 mL) was further added to the reaction mixture, and the mixture was stirred for 30 minutes and then filtered. 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 (5.75 g).

Workup

  1. customThen, the organic layer was separated
  2. washwashed with saturated saline
  3. distillationthe solvent was distilled off under reduced pressure
  4. additionA THF (50 mL) solution of the obtained residue was added to a THF (50 mL) suspension of lithium aluminum hydride (2.00 g) under ice cooling in a nitrogen atmosphere
  5. additiona 15% aqueous sodium hydroxide solution (2 mL) were added
  6. stirringthe mixture was stirred for 5 minutes
  7. additionWater (6 mL) was further added to the reaction mixture
  8. stirringthe mixture was stirred for 30 minutes
  9. filtrationfiltered
  10. concentrationThe filtrate was concentrated under reduced pressure
  11. customThe obtained residue was purified by silica gel column chromatography (hexane/ethyl acetate)

Sources & evidence

ORD record
ord-d232c9a6f38c4dafbaaa1f3f53c2cf31
Source dataset
uspto-grants-2016_05
Patent number
US09353108B2

Reaction notes

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