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

HRID 927931Notes

Reaction equation

HRID 927931 reaction equation
Br[C:2]1(Br)[CH:12]2[CH:3]1[CH2:4][O:5][C:6]1[C:11]2=[CH:10][CH:9]=[C:8]([NH:13][C:14](=[O:19])[C:15]([CH3:18])([CH3:17])[CH3:16])[C:7]=1[C:20]([O:22][CH3:23])=[O:21].[Cl-].[NH4+]>C(O)C.[Zn]>[CH3:16][C:15]([CH3:18])([CH3:17])[C:14]([NH:13][C:8]1[C:7]([C:20]([O:22][CH3:23])=[O:21])=[C:6]2[C:11]([CH:12]3[CH2:2][CH:3]3[CH2:4][O:5]2)=[CH:10][CH:9]=1)=[O:19]

Participants

5

Reactant 2

HCID 25517Ammonium ChlorideHCID 86713294Methyl 1,1-dibromo-5-(2,2-dimethylpropionylamino)-1,1a,2,7b-tetrahydrocyclopropa[c]chromene-4-carboxylate2×

Product 1

HCID 77979731Methyl (1aRS,7bSR)-5-(2,2-dimethylpropionylamino)-1,1a,2,7b-tetrahydrocyclopropa[c]chromene-4-carboxylateYield 41.7%

Reagents, catalysts & solvents 2

HCID 23994ZincCatalystHCID 702EthanolSolvent

Procedure

Methyl (1aRS,7bSR)-1,1-dibromo-5-(2,2-dimethylpropionylamino)-1,1a,2,7b-tetrahydro-cyclopropa[c]chromene-4-carboxylate (Intermediate 44, 1.13 g) was suspended in ethanol (30 mL). Zinc dust (1.17 g), followed by ammonium chloride (1.31 g) were added and the reaction mixture was heated to reflux, under an atmosphere of nitrogen, for 6 hours. After cooling, the solid was filtered off and washed with ethyl acetate. The filtrate was concentrated in vacuo and the residue was purified by chromatography on silica, eluting with a mixture of ether and cyclohexane, with a gradient of 5-12.5% to give methyl (1aRS,7bSR)-5-(2,2-dimethylpropionylamino)-1,1a,2,7b-tetrahydrocyclopropa[c]chromene-4-carboxylate (0.310 g) as a colourless oil.

Workup

  1. additionwere added
  2. temperaturethe reaction mixture was heated
  3. temperatureto reflux, under an atmosphere of nitrogen, for 6 hours
  4. temperatureAfter cooling
  5. filtrationthe solid was filtered off
  6. washwashed with ethyl acetate
  7. concentrationThe filtrate was concentrated in vacuo
  8. customthe residue was purified by chromatography on silica
  9. washeluting with a mixture of ether and cyclohexane, with a gradient of 5-12.5%

Sources & evidence

ORD record
ord-c09cffa2ccfd4e1cb053a540822dadc3
Source dataset
uspto-grants-2016_03
Patent number
US09290472B2

Reaction notes

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