Hydrochloric Acid → Ethyl 3-amino-4-(2-methoxyphenyl)-2-methylbutanoate

HRID 1281904Notes

Reaction equation

HRID 1281904 reaction equation
C[Si](C)(C)Cl.[CH3:6][O:7][C:8]1[CH:16]=[CH:15][CH:14]=[CH:13][C:9]=1[CH2:10][C:11]#[N:12].Br[CH:18]([CH3:24])[C:19]([O:21][CH2:22][CH3:23])=[O:20].[BH4-].[Na+].Cl>ClCCl.O1CCCC1.[Zn].C(O)C>[NH2:12][CH:11]([CH2:10][C:9]1[CH:13]=[CH:14][CH:15]=[CH:16][C:8]=1[O:7][CH3:6])[CH:18]([CH3:24])[C:19]([O:21][CH2:22][CH3:23])=[O:20]

Participants

10

Reactant 5

HCID 313Hydrochloric AcidHCID 6397ChlorotrimethylsilaneHCID 79040Ethyl 2-bromopropionateHCID 81496(2-Methoxyphenyl)acetonitrileHCID 4311764Sodium borohydride

Product 1

HCID 10988741Ethyl 3-amino-4-(2-methoxyphenyl)-2-methylbutanoate

Reagents, catalysts & solvents 4

HCID 23994ZincCatalystHCID 702EthanolSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

150 g of zinc in 1.5 L of absolute dichloromethane are combined with 15 mL of trimethylchlorosilane under nitrogen and stirred for 30 minutes at ambient temperature. Then 900 mL of absolute tetrahydrofuran (THF) are added and heated to 42° C. To this is added dropwise a mixture of 147 g (1.0 mol) of 2-methoxybenzylcyanide 11 and 362 g (2,0 mol) of ethyl 2-bromopropionate in 100 mL of THF and the resulting mixture is then refluxed for a further 2 h. It is left to cool, decanted off from the excess zinc and after cooling to about 5° C. combined with 70 g (1.8 mol) of sodium borohydride. Then 250 mL of ethanol are added dropwise (development of gas). The mixture is left to react for 3 h at 5° C., 1 liter of 2 N hydrochloric acid is slowly added, the phases are separated and the aqueous phase is extracted twice with 200 mL of dichloromethane. The solvent of the combined organic phase is eliminated in vacuo, the residue is combined with ice and toluene and made alkaline with conc. ammonia. The phases are separated and the aqueous phase is extracted twice more with 800 mL of toluene. The combined organic phases are dried over magnesium sulfate, and the solvent is eliminated in vacuo. Yield 149 g (61%) oil.

Workup

  1. temperatureheated to 42° C
  2. additionTo this is added dropwise
  3. temperaturethe resulting mixture is then refluxed for a further 2 h
  4. waitIt is left
  5. temperatureto cool
  6. customdecanted off from the excess zinc
  7. temperatureafter cooling to about 5° C.
  8. waitThe mixture is left
  9. customto react for 3 h at 5° C.
  10. customthe phases are separated
  11. extractionthe aqueous phase is extracted twice with 200 mL of dichloromethane
  12. customThe phases are separated
  13. extractionthe aqueous phase is extracted twice more with 800 mL of toluene
  14. dry with materialThe combined organic phases are dried over magnesium sulfate

Sources & evidence

ORD record
ord-73096ce9110943ce9eaffef5c9c50e75
Source dataset
uspto-grants-2002_09
Patent number
US06455538B1

Reaction notes

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