5-Fluoro-2-methoxyphenylboronic acid → HCID 67246860, compound

HRID 2422876Notes

Reaction equation

HRID 2422876 reaction equation
Cl.Br[C:3]1[CH:8]=[CH:7][C:6]([CH:9]([NH2:11])[CH3:10])=[C:5]([Cl:12])[CH:4]=1.[F:13][C:14]1[CH:15]=[CH:16][C:17]([O:23][CH3:24])=[C:18](B(O)O)[CH:19]=1>O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[Cl:12][C:5]1[CH:4]=[C:3]([C:16]2[CH:15]=[C:14]([F:13])[CH:19]=[CH:18][C:17]=2[O:23][CH3:24])[CH:8]=[CH:7][C:6]=1[CH:9]([NH2:11])[CH3:10]

Participants

5

Reactant 2

HCID 27826735-Fluoro-2-methoxyphenylboronic acidHCID 672440581-(4-Bromo-2-chlorophenyl)ethan-1-amine hydrochloride

Product 1

HCID 67246860HCID 67246860, compoundYield 88.9%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolvent

Conditions

Temperature
190 °C

Procedure

To a stirred solution of 4-bromo-2-chloro-acetophenone (4.66 g, 20 mmol) in methanol (50 ml) under nitrogen atmosphere was added ammonium acetate (29 g, 0.4 mol) and sodium cyanoborohydride (1.21 g, 20 mmol). The reaction mixture was stirred at ambient temperature for 10 days. The solvent was evaporated and the residue partitioned between dichloromethane and aqueous sodium carbonate solution. The organic phase was dried over anhydrous sodium sulfate and the solvent evaporated. The residue was dissolved in diethyl ether and treated with 2M Hydrogen chloride in diethyl ether The resulting precipitate was filtered and dried to give 1-(4-bromo-2-chloro-phenyl)-ethylamine hydrochloride (3.2 g). A mixture of 1-(4-bromo-2-chloro-phenyl)-ethylamine hydrochloride (0.25 g, 1.07 mmol), 5-fluoro-2-methoxyphenyl boronic acid (0.364 g, 2.14 mmol), palladium acetate (0.005 g, 0.021 mmol) in water (4 ml) was heated in a microwave oven at 190° C. for 4 min. The mixture was added to a SCX column (eluted with 1:1 dichloromethane/methanol then 10% 7M ammonia/methanol) and solvent evaporated to give 1-(3-chloro-5′-fluro-2′-methoxy-biphenyl-4-yl)-ethylamine (0.266 g). The title compound was prepared in a similar manner to N-(5′-fluoro-2,2′-dimethoxy-biphenyl-4-ylmethyl)-4-methoxy-benzenesulfonamide (Example 6) using 1-(3-chloro-5′-fluoro-2′-methoxy-biphenyl-4-yl)-ethylamine and 2-chloro-4-cyanobenzene sulfonyl chloride instead of 4-methoxybenzene sulfonyl chloride: 1H NMR (400 MHz, DMSO-d6): δ 9.1 (d 1H), 8.1 (s, 1H), 7.9 (d, 1H), 7.8 (d, 1H), 7.5 (d, 1H), 7.3 (d, 2H), 7.2 (m, 1H), 7-7.18 (m, 2H), 4.9 (m, 1H), 3.8 (s, 3H), 1.4 (d, 3H) ppm. MS (ESI) m/z: value [M+H]+.

Workup

  1. additionThe mixture was added to a SCX column (
  2. washeluted with 1:1 dichloromethane/methanol
  3. custom10% 7M ammonia/methanol) and solvent evaporated

Sources & evidence

ORD record
ord-e4f7b6efa2c64e3a8b2aa5907c0e25ba
Source dataset
uspto-grants-2011_06
Patent number
US07960365B2

Reaction notes

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