Reaction #170970

Reaction equation

6-(4-aminophenoxy)-hexanoic acid hydrochloride

6-(4-Amino-phenoxy)hexanoic acid hydrochloride

methanol

HCl

→

17

Yield 43.8%

6-(4-Aminophenoxy)-hexanoic acid methyl ester

Yield 43.8%

Conditions

Workup

1. 1
   Otherat 10° C.
2. 2
   Otherfor 1 hour
3. 3
   Temperaturerefluxed for 48 hours
4. 4
   workup.DISTILLATIONMethanol (1.5 L) was distilled off
5. 5
   workup.ADDITIONice water (1 L) was added
6. 6
   ExtractionCrude 17 was extracted into chloroform
7. 7
   Washwashed with 5% NaHCO3 solution
8. 8
   Dryingwater, and then dried over Na2SO4
9. 9
   workup.DISTILLATIONdistilled

Procedure

Method-A Through a mixture of 6-(4-aminophenoxy)-hexanoic acid hydrochloride 16 (150 g, 578 mmol) in methanol (3 L) was passed dry HCl gas at 10° C. for 1 hour and refluxed for 48 hours. Methanol (1.5 L) was distilled off, ice water (1 L) was added and the pH adjusted to 7.5 with K2CO3. Crude 17 was extracted into chloroform, washed with 5% NaHCO3 solution, then water, and then dried over Na2SO4 and distilled to give 17 (60 g, 43.8%) as a thick brown syrup. Method-B 6-(4-Nitrophenoxy)-hexanoic acid methyl ester 21 (40 g, 149.81 mmol) was dissolved in dimethyl formamide (200 ml) in a pressure vessel. Raney nickel (20 g) was added and the mixture stirred under an atmosphere of hydrogen (4 kg) for 16 hours. Catalyst was removed by filtration and dimethyl formamide distilled off under vacuum. Crude 17 was purified by column chromatography on silica gel using chloroform as eluant to get pure 17 (28 grams, 78.8%) as a thick brown syrup.

Source