Acetyl chloride → Methyl 4-(2-aminoethoxy)benzoate hydrochloride

HRID 713745Notes

Reaction equation

HRID 713745 reaction equation
C(OC(=O)[NH:7][CH2:8][CH2:9]O)(C)(C)C.[CH3:12][O:13][C:14](=[O:22])[C:15]1[CH:20]=[CH:19][C:18]([OH:21])=[CH:17][CH:16]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OC(C)C)=O)=NC(OC(C)C)=O.C([Cl:59])(=O)C>O1CCCC1>[ClH:59].[CH3:12][O:13][C:14](=[O:22])[C:15]1[CH:20]=[CH:19][C:18]([O:21][CH2:9][CH2:8][NH2:7])=[CH:17][CH:16]=1

Participants

7

Reactant 5

HCID 6367Acetyl chlorideHCID 7456MethylparabenHCID 11776TriphenylphosphineHCID 75555Diisopropyl diazene-1,2-dicarboxylateHCID 2733206tert-butyl N-(2-hydroxyethyl)carbamate

Product 1

HCID 50988568Methyl 4-(2-aminoethoxy)benzoate hydrochlorideYield 93.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
2.5 °C

Procedure

(2-Hydroxyethyl)carbamic acid tert-butyl ester (152.0 g, 0.942 mol) and 4-hydroxy-benzoic acid methyl ester (174.0 g, 1.12 mol) were dissolved in tetrahydrofuran (2000 ml) and cooled to 0-5° C. Triphenylphosphine (292.8 g 1.116 mol) was added to the cooled mixture. A solution of diisopropyl azodicarboxylate (246.0 g, 1.218 mol) in tetrahydrofuran (400 ml) was added dropwise over a period of one to two hours keeping the reaction temperature below 10° C. After addition, the reaction was allowed to warm slowly to ambient temperature and stirred overnight. After completion of reaction, solvent was distilled under reduced pressure and the resulting oil was dissolved in ethanol (500 ml) and ethyl acetate (2000 ml). Acetyl Chloride (222.0 g, 2.826 mol) was added drop wise over fifteen minutes with the temperature allowed to rise to 40° C. The resulting suspension was stirred at 40° C. until completion of reaction. After completion of reaction, the resulting crystals were filtered on a coarse frit and washed with ethyl Acetate (300 mL). The material is dried in vacuo to give of 4-(2-aminoethoxyl)benzoic acid methyl ester hydrochloride (204.1 g) as a white crystalline solid.

Workup

  1. customthe reaction temperature below 10° C
  2. additionAfter addition
  3. temperatureto warm slowly to ambient temperature
  4. customAfter completion of reaction, solvent
  5. distillationwas distilled under reduced pressure
  6. dissolutionthe resulting oil was dissolved in ethanol (500 ml)
  7. customto rise to 40° C
  8. stirringThe resulting suspension was stirred at 40° C. until completion of reaction
  9. customAfter completion of reaction
  10. filtrationthe resulting crystals were filtered on a coarse frit
  11. washwashed with ethyl Acetate (300 mL)
  12. customThe material is dried in vacuo

Sources & evidence

ORD record
ord-ca6c7bcc9d3942de9b3d4df0af580bca
Source dataset
uspto-grants-2015_11
Patent number
US09186347B1

Reaction notes

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