Sodium Carbonate → HCID 68563894, compound

HRID 20463Notes

Reaction equation

HRID 20463 reaction equation
[CH2:1]([O:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1B(O)O)[CH3:2].C(=O)([O-])[O-].[Na+].[Na+].[C:19]([O:23][C:24]([N:26]1[C@@H:31]([C@@H:32]([OH:47])[C@@H:33]([NH:43][C:44](=[O:46])[CH3:45])[CH2:34][C:35]2[CH:40]=[C:39]([F:41])[CH:38]=[C:37](Br)[CH:36]=2)[CH2:30][O:29][C@@H:28]([O:48][CH2:49][C:50]([CH3:53])([CH3:52])[CH3:51])[C@@H:27]1[CH3:54])=[O:25])([CH3:22])([CH3:21])[CH3:20]>O1CCCC1.[Pd](Cl)Cl.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2]>[C:19]([O:23][C:24]([N:26]1[C@@H:31]([C@@H:32]([OH:47])[C@@H:33]([NH:43][C:44](=[O:46])[CH3:45])[CH2:34][C:35]2[CH:40]=[C:39]([F:41])[CH:38]=[C:37]([C:5]3[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=3[O:3][CH2:1][CH3:2])[CH:36]=2)[CH2:30][O:29][C@@H:28]([O:48][CH2:49][C:50]([CH3:53])([CH3:52])[CH3:51])[C@@H:27]1[CH3:54])=[O:25])([CH3:21])([CH3:22])[CH3:20]

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 2734902(2-Ethoxyphenyl)boronic acidHCID 68561702(2R,3S,5R)-5-[(1S,2S)-1-hydroxy-2-acetylamino-3-(3-bromo-5-fluorophenyl)-propyl]-2-(2,2-dimethylpropoxy)-3-methylmorpholine-4-carboxylic acid tert-butyl ester

Product 1

HCID 68563894HCID 68563894, compoundYield 46.4%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
80 °C

Procedure

Add 2-ethoxyphenylboronic acid (0.065 g, 0.394 mmol) and (1,1′-bis(diphenylphosphino)ferrocene) palladium(II) chloride (0.021 g) to a mixture of 2M sodium carbonate solution (0.262 g, 0.525 mmol) and (2R,3S,5R)-5-[(1S,2S)-1-hydroxy-2-acetylamino-3-(3-bromo-5-fluorophenyl)-propyl]-2-(2,2-dimethylpropoxy)-3-methylmorpholine-4-carboxylic acid tert-butyl ester (0.151 g, 0.262 mmol) in tetrahydrofuran (2.62 mL) in a sealed tube flushed with nitrogen. Heat the tube at 80° C. for 3 days. Add saturated aqueous sodium chloride and extract with ethyl acetate (2×50 mL). Dry over magnesium sulfate and concentrate under reduced pressure. Subject the residue to silica gel chromatography, eluting with hexanes containing 25-50% ethyl acetate to provide the title compound (0.075 g, 46%) as a white foam.

Workup

  1. customflushed with nitrogen
  2. extractionAdd saturated aqueous sodium chloride and extract with ethyl acetate (2×50 mL)
  3. dry with materialDry over magnesium sulfate
  4. concentrationconcentrate under reduced pressure
  5. washeluting with hexanes containing 25-50% ethyl acetate

Sources & evidence

ORD record
ord-7469b8ee12ed4e0d8ea14153e71354df
Source dataset
uspto-grants-2010_06
Patent number
US07745438B2

Reaction notes

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