Citric Acid → HCID 86607736, compound

HRID 1622114Notes

Reaction equation

HRID 1622114 reaction equation
C(=O)([O-])[O-].[K+].[K+].Br[C:8]1[CH:9]=[C:10]([CH:20]=[CH:21][C:22]=1[O:23][CH2:24][O:25][CH2:26][CH2:27][O:28][CH3:29])[CH2:11][NH:12][C:13]([NH:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14].[CH3:30][O:31][CH2:32][CH2:33][O:34][CH2:35][O:36][C:37]1[C:44](B2OC(C)(C)C(C)(C)O2)=[CH:43][CH:42]=[CH:41][C:38]=1[CH:39]=[O:40].C(O)(=O)CC(CC(O)=O)(C(O)=O)O>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C(OCC)(=O)C>[C:16]([NH:15][C:13]([NH:12][CH2:11][C:10]1[CH:9]=[C:8]([C:44]2[CH:43]=[CH:42][CH:41]=[C:38]([CH:39]=[O:40])[C:37]=2[O:36][CH2:35][O:34][CH2:33][CH2:32][O:31][CH3:30])[C:22]([O:23][CH2:24][O:25][CH2:26][CH2:27][O:28][CH3:29])=[CH:21][CH:20]=1)=[O:14])([CH3:19])([CH3:18])[CH3:17]

Participants

7

Reactant 4

HCID 311Citric AcidHCID 11430Potassium CarbonateHCID 66986052HCID 66986052, compoundHCID 86607704HCID 86607704, compound

Product 1

HCID 86607736HCID 86607736, compoundYield 56.4%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 8857Ethyl AcetateSolvent

Procedure

A 2 M solution of potassium carbonate (2.1 mL) was added to a magnetically stirred mixture of 1-[3-bromo-4-(2-methoxyethoxymethoxy)benzyl]-3-tert-butylurea (1.4 g, 4.1 mmol), prepared as in Reference 11, and 2-(2-methoxyethoxymethoxy)-3-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzaldehyde (42 mL, 0.1 mM in toluene, 4.2 mmol), prepared as in Reference 15. The mixture was flushed with nitrogen and then tetrakis(triphenylphosphine)palladium(0) (118 mg, 0.1025 mmol) was added. The mixture was refluxed for 7 hours, cooled and then poured into a mixture of ethyl acetate and 5% citric acid. The organic phase was separated and the aqueous phase was extracted twice more with ethyl acetate. The combined organic phase was dried and concentrated by evaporation. Product was purified from the residue by chromatography on silica gel utilizing 100% ethyl acetate to give 1-tert-butyl-3-[3′-formyl-6,2′-bis-(2-methoxyethoxymethoxy)-biphenyl-3-ylmethyl]-urea (1.2 g).

Workup

  1. customThe mixture was flushed with nitrogen
  2. temperatureThe mixture was refluxed for 7 hours
  3. temperaturecooled
  4. customThe organic phase was separated
  5. extractionthe aqueous phase was extracted twice more with ethyl acetate
  6. customThe combined organic phase was dried
  7. concentrationconcentrated by evaporation
  8. customProduct was purified from the residue by chromatography on silica gel utilizing 100% ethyl acetate

Sources & evidence

ORD record
ord-3716b1e49a814945b5e811ee6f781cef
Source dataset
uspto-grants-2014_07
Patent number
US08778625B2

Reaction notes

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