Methyl (1aRS,7bSR)-5-(2,2-dimethylpropionylamino)-1,1a,2,7b-tetrahydrocyclopropa[c]chromene-4-carboxylate → Methyl 5-amino-1,1a,2,7b-tetrahydrocyclopropa[c]chromene-4-carboxylate

HRID 927930Notes

Reaction equation

HRID 927930 reaction equation
CC(C)(C)C([NH:5][C:6]1[C:15]([C:16]([O:18][CH3:19])=[O:17])=[C:14]2[C:9]([CH:10]3[CH2:20][CH:11]3[CH2:12][O:13]2)=[CH:8][CH:7]=1)=O>CO.S(=O)(=O)(O)O>[NH2:5][C:6]1[C:15]([C:16]([O:18][CH3:19])=[O:17])=[C:14]2[C:9]([CH:10]3[CH2:20][CH:11]3[CH2:12][O:13]2)=[CH:8][CH:7]=1

Participants

4

Reactant 1

HCID 77979731Methyl (1aRS,7bSR)-5-(2,2-dimethylpropionylamino)-1,1a,2,7b-tetrahydrocyclopropa[c]chromene-4-carboxylate2×

Product 1

HCID 86713293Methyl 5-amino-1,1a,2,7b-tetrahydrocyclopropa[c]chromene-4-carboxylateYield 53.6%

Reagents, catalysts & solvents 2

HCID 1118Sulfuric AcidCatalyst2×HCID 887MethanolSolvent

Procedure

Methyl (1aRS,7bSR)-5-(2,2-dimethylpropionylamino)-1,1a,2,7b-tetrahydrocyclopropa[c]chromene-4-carboxylate (Intermediate 43, 0.310 g) was suspended in methanol (7.5 mL) and concentrated sulphuric acid (4 drops) was added. The reaction mixture was heated to reflux, under an atmosphere of nitrogen, for 36 hours. A further 2 drops of concentrated sulphuric acid was added and heating was continued for a further 24 hours. After cooling, the mixture was concentrated in vacuo and the residue was partitioned between ethyl acetate and saturated aqueous potassium carbonate solution. The aqueous layer was extracted with ethyl acetate and the combined organic layers were dried (Na2SO4) and filtered. The filtrate was concentrated in vacuo and the residue was purified by chromatography on silica, eluting with a mixture of ethyl acetate and cyclohexane, with a gradient of 5-20% to give methyl (1aRS,7bSR)-5-amino-1,1a,2,7b-tetrahydrocyclopropa[c]chromene-4-carboxylate (0.120 g) as an off-white solid.

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureto reflux, under an atmosphere of nitrogen, for 36 hours
  3. temperatureheating
  4. temperatureAfter cooling
  5. concentrationthe mixture was concentrated in vacuo
  6. customthe residue was partitioned between ethyl acetate and saturated aqueous potassium carbonate solution
  7. extractionThe aqueous layer was extracted with ethyl acetate
  8. dry with materialthe combined organic layers were dried (Na2SO4)
  9. filtrationfiltered
  10. concentrationThe filtrate was concentrated in vacuo
  11. customthe residue was purified by chromatography on silica
  12. washeluting with a mixture of ethyl acetate and cyclohexane, with a gradient of 5-20%

Sources & evidence

ORD record
ord-317f7cd9409745d68db0a8389e3bec33
Source dataset
uspto-grants-2016_03
Patent number
US09290472B2

Reaction notes

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