Hydrochloric Acid → 2-(3,4-Bis(2-(tert-butoxycarbonylamino)ethoxy)phenyl)acetic acid

HRID 2208617

Reaction equation

HRID 2208617 reaction equation
[OH:1][C:2]1[CH:3]=[C:4]([CH2:9][C:10]([O:12]C)=[O:11])[CH:5]=[CH:6][C:7]=1[OH:8].Br[CH2:15][CH2:16][NH:17][C:18](=[O:24])[O:19][C:20]([CH3:23])([CH3:22])[CH3:21].[C:25]([O-:28])([O-])=[O:26].[K+].[K+].[OH-].[Na+].Cl>CN(C=O)C.CO.C1COCC1.O>[C:20]([O:19][C:18]([NH:17][CH2:16][CH2:15][O:1][C:2]1[CH:3]=[C:4]([CH2:9][C:10]([OH:12])=[O:11])[CH:5]=[CH:6][C:7]=1[O:8][CH2:15][CH2:16][NH:17][C:25]([O:28][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:26])=[O:24])([CH3:23])([CH3:22])[CH3:21]

Participants

10

Reactant 5

HCID 313Hydrochloric AcidHCID 11430Potassium CarbonateHCID 14798Sodium HydroxideHCID 4103526tert-Butyl N-(2-bromoethyl)carbamateHCID 11008556Methyl 3,4-Dihydroxyphenylacetate

Product 1

HCID 867252812-(3,4-Bis(2-(tert-butoxycarbonylamino)ethoxy)phenyl)acetic acid

Reagents, catalysts & solvents 4

HCID 887MethanolSolventHCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

To methyl 2-(3,4-dihydroxyphenyl)acetate (1.0 g) in DMF (10 mL) was added tert-butyl 2-bromoethylcarbamate (2.7 g) and K2CO3 (1.7 g). The resulting reaction mixture was stirred at 60° C. overnight. Water was added and the aqueous phase extracted with EtOAc. The organic phase was then dried and concentrated. The residue was purified by flash chromatography. The product was obtained as a mixture of mono- and bis-alkylation. The mixture was then dissolved in MeOH and THF (10 mL, 1:1) and 1N NaOH was added. The resulting reaction mixture was stirred at room temperature overnight. 1N HCl was added to acidify the solution. The aqueous phase was extracted with EtOAc (3×). The organic phases were combined, dried and concentrated. The title product was obtained by reverse phase chromatography purification (0.5 g).

Workup

  1. customThe resulting reaction mixture
  2. extractionthe aqueous phase extracted with EtOAc
  3. customThe organic phase was then dried
  4. concentrationconcentrated
  5. customThe residue was purified by flash chromatography
  6. customThe product was obtained as a mixture of mono- and bis-alkylation
  7. customThe resulting reaction mixture
  8. stirringwas stirred at room temperature overnight
  9. extractionThe aqueous phase was extracted with EtOAc (3×)
  10. customdried
  11. concentrationconcentrated

Sources & evidence

ORD record
ord-d09d0bcf3b3f4d62b9cc61b04f6ed12e
Source dataset
uspto-grants-2016_06
Patent number
US09376454B2

Linked notes

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