Potassium Carbonate → Methyl 4-[2(R)-amino-1-propoxy]phenylacetate

HRID 1901209Notes

Reaction equation

HRID 1901209 reaction equation
N(C(OCC)=O)=NC(OCC)=O.C(OC([NH:20][C@H:21]([CH3:24])[CH2:22][OH:23])=O)(C)(C)C.O[C:26]1[CH:31]=[CH:30][C:29]([CH2:32][C:33]([O:35][CH3:36])=[O:34])=[CH:28][CH:27]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(=O)([O-])[O-].[K+].[K+]>C1C=CC=CC=1.O>[NH2:20][C@H:21]([CH3:24])[CH2:22][O:23][C:26]1[CH:31]=[CH:30][C:29]([CH2:32][C:33]([O:35][CH3:36])=[O:34])=[CH:28][CH:27]=1

Participants

8

Reactant 5

HCID 11430Potassium CarbonateHCID 11776TriphenylphosphineHCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 518900Benzeneacetic acid, 4-hydroxy-, methyl esterHCID 13200309tert-butyl N-((2R)-1-hydroxypropan-2-yl)carbamate

Product 1

HCID 22867083Methyl 4-[2(R)-amino-1-propoxy]phenylacetate

Reagents, catalysts & solvents 2

HCID 241BenzeneSolventHCID 962WaterSolvent

Procedure

16.6 g of diethyl azodicarboxylate were added, whilst ice-cooling, to a solution of 16.8 g of (R)-2-t-butoxycarbonylamino-1-propanol, 10.0 g of methyl 4-hydroxyphenylacetate and 24.0 g of triphenylphosphine in 50 ml of dry benzene, and the resulting mixture was stirred at room temperature for 2 days. At the end of this time, the benzene solvent was removed by distillation under reduced pressure. The resulting residue was dissolved in 100 ml of methanol, and 200 ml of a 4N solution of hydrogen chloride in dioxane were added to the solution thus obtained, whilst ice-cooling, after which the mixture was allowed to stand at room temperature for 3 hours. The reaction mixture was then poured into water, and the pH of the aqueous mixture was adjusted to a value of 8 to 9 by the addition of an aqueous solution of potassium carbonate, and then the mixture was extracted with ethyl acetate. The extract was dried over anhydrous sodium sulfate, and the ethyl acetate solvent was removed by distillation under reduced pressure. The resulting residue was purified by column chromatography through silica gel, using a 3:1 by volume mixture of ethyl acetate and ethanol as the eluent, to give the title compound.

Workup

  1. customAt the end of this time, the benzene solvent was removed by distillation under reduced pressure
  2. dissolutionThe resulting residue was dissolved in 100 ml of methanol
  3. addition200 ml of a 4N solution of hydrogen chloride in dioxane were added to the solution
  4. customthus obtained
  5. temperaturewhilst ice-cooling
  6. waitto stand at room temperature for 3 hours
  7. extractionthe mixture was extracted with ethyl acetate
  8. dry with materialThe extract was dried over anhydrous sodium sulfate
  9. customthe ethyl acetate solvent was removed by distillation under reduced pressure
  10. customThe resulting residue was purified by column chromatography through silica gel
  11. additionby volume mixture of ethyl acetate and ethanol as the eluent

Sources & evidence

ORD record
ord-4cc11b49dfd54704af828866314b5f79
Source dataset
uspto-grants-1996_11
Patent number
US05576340

Reaction notes

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