Hydrochloric Acid → (1R,2S)-2-(4-(Benzyloxy)phenyl)cyclopropan-1-amine

HRID 1023812Notes

Reaction equation

HRID 1023812 reaction equation
[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([C@@H:15]2[CH2:17][C@H:16]2[N+:18]([O-])=O)=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl>CC(O)C.[Zn]>[CH2:1]([O:8][C:9]1[CH:10]=[CH:11][C:12]([C@@H:15]2[CH2:17][C@H:16]2[NH2:18])=[CH:13][CH:14]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 2

HCID 313Hydrochloric AcidHCID 666290981-(Benzyloxy)-4-[(trans)-2-nitrocyclopropyl]benzene2×

Product 1

HCID 51888238(1R,2S)-2-(4-(Benzyloxy)phenyl)cyclopropan-1-amineYield 70%

Reagents, catalysts & solvents 2

HCID 23994ZincCatalystHCID 3776IsopropanolSolvent

Procedure

Zn dust (1.97 g, 30 mol) was added in small portions, over a period of 30 min, to a vigorously stirred solution of 1-(benzyloxy)-4-[(trans)-2-nitrocyclopropyl]benzene (Intermediate C, 0.81 g, 3.0 mmol) in i-PrOH (25 mL) and HCl (11 mL of aqueous solution 2.7 N, 30 mmol). After 17 h the mixture was filtered through a pad of celite that was washed with 10 mL of methanol. The filtrate was concentrated and 10 mL of water were added, washing with CH2Cl2 (3×15 mL). The organic layers were dried over anhydrous Na2SO4 and filtered. After removal of the solvent, the crude product was purified by column chromatography on silica gel (10% MeOH/CH2Cl2) affording 0.50 g of (trans)-2-[4-(benzyloxy)phenyl]cyclopropanamine [Rf=0.2 (10% MeOH/CH2Cl2), white solid, 70% yield]. 1H NMR δ (ppm): MeO 400 MH: 7.45-7.27 (m, 5H, ArH); 6.96 (d, J=8.5 Hz, 2H, ArH); 6.86 (d, J=8.5 Hz, 2H, ArH); 5.03 (s, 2H, CH2); 2.41-2.34 (m, 1H, CH); 1.86-1.76 (m, 1H, CH); 0.98-0.85 (m, 2H, CH2).

Workup

  1. filtrationAfter 17 h the mixture was filtered through a pad of celite that
  2. washwas washed with 10 mL of methanol
  3. concentrationThe filtrate was concentrated
  4. addition10 mL of water were added
  5. washwashing with CH2Cl2 (3×15 mL)
  6. dry with materialThe organic layers were dried over anhydrous Na2SO4
  7. filtrationfiltered
  8. customAfter removal of the solvent
  9. customthe crude product was purified by column chromatography on silica gel (10% MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-226012d32afe419c89e5a40bf76c12b4
Source dataset
uspto-grants-2014_05
Patent number
US08722743B2

Reaction notes

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