Diethylamine → methyl (1aRS,7bSR)-5-{N-(methoxycarbonyl)-N-[2((Z)-4-diethylaminobut-1-enyl)-4-fluorobenzenesulfonyl]amino}-1,1a,2,7b-tetrahydrocyclopropa-[c]chromene-4-carboxylate

HRID 927958Notes

Reaction equation

HRID 927958 reaction equation
CS(OS(C)(=O)=O)(=O)=O.[CH3:10][O:11][C:12]([N:14]([C:30]1[C:39]([C:40]([O:42][CH3:43])=[O:41])=[C:38]2[C:33]([CH:34]3[CH2:44][CH:35]3[CH2:36][O:37]2)=[CH:32][CH:31]=1)[S:15]([C:18]1[CH:23]=[CH:22][C:21]([F:24])=[CH:20][C:19]=1/[CH:25]=[CH:26]\[CH2:27][CH2:28]O)(=[O:17])=[O:16])=[O:13].[CH:45]([N:48](C(C)C)[CH2:49][CH3:50])(C)[CH3:46].C(NCC)C>C(Cl)Cl.O>[CH3:10][O:11][C:12]([N:14]([C:30]1[C:39]([C:40]([O:42][CH3:43])=[O:41])=[C:38]2[C:33]([CH:34]3[CH2:44][CH:35]3[CH2:36][O:37]2)=[CH:32][CH:31]=1)[S:15]([C:18]1[CH:23]=[CH:22][C:21]([F:24])=[CH:20][C:19]=1/[CH:25]=[CH:26]\[CH2:27][CH2:28][N:48]([CH2:49][CH3:50])[CH2:45][CH3:46])(=[O:17])=[O:16])=[O:13]

Participants

7

Reactant 4

HCID 8021DiethylamineHCID 81531DiisopropylethylamineHCID 81560Methanesulfonic anhydrideHCID 86713307Methyl (1aRS,7bSR)-5-{N-[methoxycarbonyl]-N-[2-((Z)-4-hydroxybut-1-enyl)-4-fluorobenzenesulfonyl]amino}-1,1a,2,7b-tetrahydrocyclopropa[c]chromene-4-carboxylate2×

Product 1

HCID 90086604methyl (1aRS,7bSR)-5-{N-(methoxycarbonyl)-N-[2((Z)-4-diethylaminobut-1-enyl)-4-fluorobenzenesulfonyl]amino}-1,1a,2,7b-tetrahydrocyclopropa-[c]chromene-4-carboxylateYield 60.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

Methyl sulfonic anhydride (0.062 g) was added to a stirred, cooled mixture of methyl (1aRS,7bSR)-5-{N-[methoxycarbonyl]-N-[2-((Z)-4-hydroxybut-1-enyl)-4-fluorobenzene-sulfonyl]amino}-1,1a,2,7b-tetrahydrocyclopropa[c]chromene-4-carboxylate (Intermediate 73, 0.12 g) and N,N-di-isopropyl-N-ethylamine (0.046 g) in DCM (15 mL) at 0° C. The resultant mixture was stirred at 0° C. for 20 minutes. Diethylamine (0.026 g) was added and the mixture was then stirred at room temperature for 24 hours. The mixture was diluted with water and extracted with DCM, dried (Na2SO4) and filtered. The filtrate was evaporated to dryness and the residue was purified by chromatography on silica, eluting with a mixture of methanol and DCM with a gradient of 2-10% to give methyl (1aRS,7bSR)-5-{N-(methoxycarbonyl)-N-[2((Z)-4-diethylaminobut-1-enyl)-4-fluorobenzenesulfonyl]amino}-1,1a,2,7b-tetrahydrocyclopropa-[c]chromene-4-carboxylate (0.08 g) as alight yellow solid.

Workup

  1. temperaturecooled
  2. extractionextracted with DCM
  3. dry with materialdried (Na2SO4)
  4. filtrationfiltered
  5. customThe filtrate was evaporated to dryness
  6. customthe residue was purified by chromatography on silica
  7. washeluting with a mixture of methanol and DCM with a gradient of 2-10%

Sources & evidence

ORD record
ord-dfa2be822814449a8245921e9eb5ad85
Source dataset
uspto-grants-2016_03
Patent number
US09290472B2

Reaction notes

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