HCID 57705843, compound → Ethyl 3-(5-(((2-(1,1-dimethylethyl)-2'-fluoro-5'-(methyloxy)-1,1'-biphenyl-4-yl)methyl)oxy)-3-pyridinyl)propanoate

HRID 1662577

Reaction equation

HRID 1662577 reaction equation
Br[C:2]1[CH:3]=[N:4][CH:5]=[C:6]([O:8][CH2:9][C:10]2[CH:15]=[CH:14][C:13]([C:16]3[CH:21]=[C:20]([O:22][CH3:23])[CH:19]=[CH:18][C:17]=3[F:24])=[C:12]([C:25]([CH3:28])([CH3:27])[CH3:26])[CH:11]=2)[CH:7]=1.[Br-].[CH2:30]([O:32][C:33](=[O:37])[CH2:34][CH2:35][Zn+])[CH3:31]>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].CC(P(C(C)(C)C)[C]1[CH][CH][CH][CH]1)(C)C.C1C=CC([C]2[C](C3C=CC=CC=3)[C](C3C=CC=CC=3)[C](C3C=CC=CC=3)[C]2C2C=CC=CC=2)=CC=1.[Fe].C1COCC1>[CH3:26][C:25]([C:12]1[CH:11]=[C:10]([CH2:9][O:8][C:6]2[CH:7]=[C:2]([CH2:35][CH2:34][C:33]([O:32][CH2:30][CH3:31])=[O:37])[CH:3]=[N:4][CH:5]=2)[CH:15]=[CH:14][C:13]=1[C:16]1[CH:21]=[C:20]([O:22][CH3:23])[CH:19]=[CH:18][C:17]=1[F:24])([CH3:28])[CH3:27]

Participants

6

Reactant 2

HCID 57705843HCID 57705843, compoundHCID 178471816HCID 178471816, compound

Product 1

HCID 57706385Ethyl 3-(5-(((2-(1,1-dimethylethyl)-2'-fluoro-5'-(methyloxy)-1,1'-biphenyl-4-yl)methyl)oxy)-3-pyridinyl)propanoateYield 61%

Reagents, catalysts & solvents 3

HCID 6505921(1E,4E)-1,5-diphenylpenta-1,4-dien-3-one; palladiumCatalystHCID 178454872HCID 178454872, compoundCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
80 °C

Procedure

To a sealed tube containing 96.A (0.2020 g, 0.455 mmol), bis(dibenzylideneacetone)palladium(0) (0.0141 g, 0.0245 mmol), and CTC-Q-Phos (0.0168 g, 0.0236 mmol) was added dry THF (3 mL). After 5 minutes, 3-ethoxy-3-oxopropylzinc bromide (2.0 mL, 1.00 mmol) (0.5 M solution in THF) was added. After 1 hour, the mixture was heated to 80° C. and monitored with TLC and LC-MS. After 16.5 hours, the reaction was cooled to room temperature, and the organic solvent was removed under reduced pressure. The residue was purified by silica gel flash chromatography (0-40% EtOAc/hexane) to afford 96.B which was used without further purification (129.1 mg, 61% yield). MS ESI (pos.) m/e: 466.3 (M+H)+.

Workup

  1. waitAfter 1 hour
  2. waitAfter 16.5 hours
  3. temperaturethe reaction was cooled to room temperature
  4. customthe organic solvent was removed under reduced pressure
  5. customThe residue was purified by silica gel flash chromatography (0-40% EtOAc/hexane)

Sources & evidence

ORD record
ord-153a2d7b30454173abbf1696cf23e331
Source dataset
uspto-grants-2011_10
Patent number
US08030354B2

Linked notes

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