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

HRID 1478885

Reaction equation

HRID 1478885 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+].O>CN(C=O)C.CO.[OH-].[Na+].Cl.C1COCC1>[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 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 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 5

HCID 313Hydrochloric AcidSolventHCID 887MethanolSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolventHCID 14798Sodium HydroxideSolvent

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 IN NaOH was added. The resulting reaction mixture was stirred at room temperature overnight. IN 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-c12e81b672324999a5c61d59ee958931
Source dataset
uspto-grants-2016_08
Patent number
US09403850B2

Linked notes

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