Methanol → 2'-Methyl-2',3'-dihydro-1'H-spiro[cyclopropane-1,4'-isoquinolin]-7'-amine

HRID 1891039Notes

Reaction equation

HRID 1891039 reaction equation
Cl.Cl.[CH3:3][N:4]1[CH2:13][C:12]2([CH2:15][CH2:14]2)[C:11]2[C:6](=[CH:7][C:8]([NH2:16])=[CH:9][CH:10]=2)[CH2:5]1.[OH-].[Na+].CO>C(Cl)(Cl)Cl>[CH3:3][N:4]1[CH2:13][C:12]2([CH2:15][CH2:14]2)[C:11]2[C:6](=[CH:7][C:8]([NH2:16])=[CH:9][CH:10]=2)[CH2:5]1

Participants

5

Reactant 3

HCID 887MethanolHCID 14798Sodium HydroxideHCID 670752002'-methyl-2',3'-dihydro-1'H-spiro[cyclopropane-1,4'-isoquinolin]-7'-amine dihydrochloride

Product 1

HCID 445958982'-Methyl-2',3'-dihydro-1'H-spiro[cyclopropane-1,4'-isoquinolin]-7'-amineYield 102.3%

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Procedure

To a stirred suspension of 2′-methyl-2′,3′-dihydro-1′H-spiro[cyclopropane-1,4′-isoquinolin]-7′-amine dihydrochloride (1.90 kg, 7.27 mol, 1.09 eq.) in chloroform (19 L) at room temperature was added 5 N NaOH (3.8 L), and the mixture was stirred for 5 minutes. The chloroform layer was separated and the aqueous layer was extracted with chloroform (9.5 L). Combined chloroform layers were washed with 5% aqueous NaCl (9.5 L), then dried over anhydrous sodium sulfate (3.8 kg) for 1 hour. Sodium sulfate was filtered and washed with chloroform (3.8 L). Combined filtrate and washing were evaporated to give crude oil. Methanol (4.6 L) was added and the solution was evaporated to give 2′-methyl-2′,3′-dihydro-1′H-spiro[cyclopropane-1,4′-isoquinolin]-7′-amine (1.40 kg) as brownish crystals in crude 102% recovery.

Workup

  1. customThe chloroform layer was separated
  2. extractionthe aqueous layer was extracted with chloroform (9.5 L)
  3. washCombined chloroform layers were washed with 5% aqueous NaCl (9.5 L)
  4. dry with materialdried over anhydrous sodium sulfate (3.8 kg) for 1 hour
  5. filtrationSodium sulfate was filtered
  6. washwashed with chloroform (3.8 L)
  7. washCombined filtrate and washing
  8. customwere evaporated
  9. customto give crude oil
  10. customthe solution was evaporated

Sources & evidence

ORD record
ord-0b78ec0e26a64123bf8d6683758c7a4c
Source dataset
uspto-grants-2013_08
Patent number
US08507504B2

Reaction notes

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