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

HRID 927932Notes

Reaction equation

HRID 927932 reaction equation
[CH3:1][C:2]([CH3:21])([CH3:20])[C:3]([NH:5][C:6]1[C:15]([C:16]([O:18][CH3:19])=[O:17])=[C:14]2[C:9]([CH:10]=[CH:11][CH2:12][O:13]2)=[CH:8][CH:7]=1)=[O:4].[OH-].[Na+].[CH:24](Br)([Br:26])[Br:25]>[Cl-].C([N+](CC)(CC)CC)C1C=CC=CC=1>[Br:25][C:24]1([Br:26])[CH:10]2[CH:11]1[CH2:12][O:13][C:14]1[C:9]2=[CH:8][CH:7]=[C:6]([NH:5][C:3](=[O:4])[C:2]([CH3:21])([CH3:20])[CH3:1])[C:15]=1[C:16]([O:18][CH3:19])=[O:17]

Participants

5

Reactant 3

HCID 5558BromoformHCID 14798Sodium HydroxideHCID 70983794Methyl 7-pivalamido-2H-chromene-8-carboxylate2×

Product 1

HCID 86713294Methyl 1,1-dibromo-5-(2,2-dimethylpropionylamino)-1,1a,2,7b-tetrahydrocyclopropa[c]chromene-4-carboxylate

Reagents, catalysts & solvents 1

HCID 66133Benzyl triethylammonium chlorideCatalyst

Conditions

Temperature
60 °C

Procedure

Methyl 7-(2,2-dimethylpropionylamino)-2H-chromene-8-carboxylate (Intermediate 45, 2.372 g) and benzyl triethyl ammonium chloride (0.373 g) were suspended in bromoform (6.45 mL) and aqueous sodium hydroxide solution (50%, 3.64 mL) was added dropwise. The resultant black suspension was heated to 60° C. for 2 hours. After cooling, the mixture was partitioned between water and ethyl acetate. The emulsion formed was filtered through a pad of Celite and the organic layer was decanted off. The aqueous was re-extracted with ethyl acetate and the combined organic layers were dried (MgSO4) 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 2.5-15% to give methyl 1,1-dibromo-5-(2,2-dimethylpropionylamino)-1,1a,2,7b-tetrahydrocyclopropa[c]chromene-4-carboxylate (1.557 g) as an off-white solid.

Workup

  1. temperatureAfter cooling
  2. customthe mixture was partitioned between water and ethyl acetate
  3. customThe emulsion formed
  4. filtrationwas filtered through a pad of Celite
  5. customthe organic layer was decanted off
  6. extractionThe aqueous was re-extracted with ethyl acetate
  7. dry with materialthe combined organic layers were dried (MgSO4)
  8. filtrationfiltered
  9. concentrationThe filtrate was concentrated in vacuo
  10. customthe residue was purified by chromatography on silica
  11. washeluting with a mixture of ethyl acetate and cyclohexane, with a gradient of 2.5-15%

Sources & evidence

ORD record
ord-0e10eedb83ba40339fe25a78c95f22c6
Source dataset
uspto-grants-2016_03
Patent number
US09290472B2

Reaction notes

Loading…