Sodium Carbonate → HCID 57504912, compound

HRID 2060783Notes

Reaction equation

HRID 2060783 reaction equation
[CH2:1]([N:8]1[C:12]2([C:24]3[CH:29]=[CH:28][CH:27]=[C:26](Br)[CH:25]=3)[CH2:13][CH:14]([O:16][Si:17]([C:20]([CH3:23])([CH3:22])[CH3:21])([CH3:19])[CH3:18])[CH2:15][CH:11]2[CH2:10][O:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(=O)([O-])[O-].[Na+].[Na+].[CH3:37][O:38][C:39]1[CH:40]=[C:41](B(O)O)[CH:42]=[CH:43][CH:44]=1>COCCOC.C(OCC)(=O)C>[CH2:1]([N:8]1[C:12]2([C:24]3[CH:25]=[C:26]([C:43]4[CH:42]=[CH:41][CH:40]=[C:39]([O:38][CH3:37])[CH:44]=4)[CH:27]=[CH:28][CH:29]=3)[CH2:13][CH:14]([O:16][Si:17]([C:20]([CH3:23])([CH3:22])[CH3:21])([CH3:19])[CH3:18])[CH2:15][CH:11]2[CH2:10][O:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 2734370(3-Methoxyphenyl)boronic acidHCID 57504911HCID 57504911, compound

Product 1

HCID 57504912HCID 57504912, compoundYield 96.8%

Reagents, catalysts & solvents 2

HCID 80711,2-DimethoxyethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
110 °C

Procedure

To a stirred solution of 1-benzyl-6a-(3-bromophenyl)-5-(tert-butyldimethylsilyloxy)hexahydro-1H-cyclopenta[c]isoxazole (7.42 g, 15.2 mmol) in 1,2-dimethoxyethane (30 mL) is added 2 M aqueous solution of sodium carbonate (22.8 mL, 45.6 mmol), 3-methoxyphenylboronic acid (2.77 g, 18.2 mmol) and (1,1′-bis(diphenylphosphino)ferrocene)palladium(II) chloride (0.759 g, 0.911 mmol). The reaction mixture is heated at 110° C. for 7 hours. The reaction is cooled, diluted with ethyl acetate, and filtered. The resulting filtrate is separated and the aqueous layer is extracted three times with ethyl acetate. The combined organic layers are washed with brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure. The crude product is purified by silica gel chromatography eluting with 10% to 20% ethyl acetate in hexanes gradient over 20 minutes to give the title compound (7.59 g, 92%). ES/MS m/e: 516 (M+1).

Workup

  1. temperatureThe reaction is cooled
  2. filtrationfiltered
  3. customThe resulting filtrate is separated
  4. extractionthe aqueous layer is extracted three times with ethyl acetate
  5. washThe combined organic layers are washed with brine
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe crude product is purified by silica gel chromatography
  10. washeluting with 10% to 20% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-063fa42664c44f07b6e36b03bfd22a22
Source dataset
uspto-grants-2012_10
Patent number
US08278441B2

Reaction notes

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