HCID 92135481, compound → HCID 117607191, compound

HRID 588881Notes

Reaction equation

HRID 588881 reaction equation
[NH2:1][C:2]1[CH:7]=[C:6](I)[C:5]([Cl:9])=[CH:4][C:3]=1[OH:10].[CH:11]1([Mg]Br)[CH2:13][CH2:12]1>C1COCC1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[NH2:1][C:2]1[CH:7]=[C:6]([CH:11]2[CH2:13][CH2:12]2)[C:5]([Cl:9])=[CH:4][C:3]=1[OH:10]

Participants

5

Reactant 2

HCID 92135481HCID 92135481, compoundHCID 178418630HCID 178418630, compound

Product 1

HCID 117607191HCID 117607191, compoundYield 63.1%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 8028TetrahydrofuranSolvent

Procedure

To a mixture of 2-amino-5-chloro-4-iodophenol (500 mg, 1.9 mmol), PdCl2(dppf) (136 mg, 0.19 mmol) in THF (10 mL) under argon at RT, cyclopropylmagnesium bromide (16 mL, 11.4 mmol, 0.7 M in THF) was added and the mixture was stirred at reflux for 15 h. The mixture was allowed to cool to RT, and partitioned between ethyl acetate and water. The organic layer was washed with brine, dried over Na2SO4 and concentrated. The residue was purified by flash column chromatography on silica gel (10-20% ethyl acetate/hexanes) to afford the desired product (220 mg, 63% yield) as a brown solid. 1H NMR (400 MHz, DMSO-d6) δ: 9.27 (s, 1H), 6.62 (s, 1H), 6.22 (s, 1H), 4.53 (s, 2H), 1.89-1.93 (m, 1H), 0.83-0.87 (m, 2H), 0.46-0.49 (m, 2H).

Workup

  1. temperatureat reflux for 15 h
  2. custompartitioned between ethyl acetate and water
  3. washThe organic layer was washed with brine
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated
  6. customThe residue was purified by flash column chromatography on silica gel (10-20% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-605e8c3cc6774f50aaa91981b553ad1b
Source dataset
uspto-grants-2016_01
Patent number
US09227978B2

Reaction notes

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