Reaction #1833273

Reaction equation

NaOH

1-((2-methoxyethoxy)methoxy)-4-((trans)-2-nitrocyclopropyl)benzene

Intermediate K

1-((2-methoxyethoxy)methoxy)-4-((trans)-2-nitrocyclopropyl)benzene

HCl

→

(trans)-2-(4-((2-methoxyethoxy)methoxy)phenyl)cyclopropanamine

Yield 73.0%

Solvents

i-PrOH

Conditions

Workup

1. 1
   Filtrationfiltered through a pad of celite, that
2. 2
   Washwas washed with 10 mL of methanol
3. 3
   ConcentrationThe filtrate was concentrated
4. 4
   workup.ADDITION15 mL of water were added
5. 5
   Extractionextracting with CH2Cl2 (3×15 mL)
6. 6
   Washthe organic layers were washed with brine (25 mL)
7. 7
   Dryingdried over anhydrous Na2SO4
8. 8
   Filtrationfiltered
9. 9
   OtherAfter removal of the solvent
10. 10
    Otherthe crude product was purified by column chromatography on silica gel (2-5% MeOH/CH2Cl2)

Procedure

Zn dust (0.99 g, 15.1 mol) was added in small portions, over a period of 20 min, to a vigorously stirred solution of 1-((2-methoxyethoxy)methoxy)-4-((trans)-2-nitrocyclopropyl)benzene (Intermediate K, 0.40 g, 1.51 mmol) in i-PrOH (15 mL) and HCl (5.6 mL of 2.7 N aqueous solution, 15.1 mmol). After 16 h, the mixture was basified with NaOH (10% aqueous solution, 10 mL) and filtered through a pad of celite, that was washed with 10 mL of methanol. The filtrate was concentrated and 15 mL of water were added, extracting with CH2Cl2 (3×15 mL); the organic layers were washed with brine (25 mL), dried over anhydrous Na2SO4 and filtered. After removal of the solvent, the crude product was purified by column chromatography on silica gel (2-5% MeOH/CH2Cl2) affording 0.26 g of (trans)-2-(4-((2-methoxyethoxy)methoxy)phenyl)cyclopropanamine [Rf=0.1 (5% MeOH/CH2Cl2), white solid, 73% yield].

Source