Methyl chloroformate → methyl (1aRS,7bSR)-5-[N-(methoxycarbonyl)-N-(4-fluoro-2-nitrobenzene-sulfonyl)amino]-1,1a,2,7b-tetrahydro-cyclopropa[c]chromene-4-carboxylate

HRID 927991Notes

Reaction equation

HRID 927991 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([NH:11][C:12]2[C:21]([C:22]([O:24][CH3:25])=[O:23])=[C:20]3[C:15]([CH:16]4[CH2:26][CH:17]4[CH2:18][O:19]3)=[CH:14][CH:13]=2)(=[O:10])=[O:9])=[C:4]([N+:27]([O-:29])=[O:28])[CH:3]=1.[H-].[Na+].Cl[C:33]([O:35][CH3:36])=[O:34].C(=O)(O)[O-].[Na+]>C1COCC1>[CH3:36][O:35][C:33]([N:11]([C:12]1[C:21]([C:22]([O:24][CH3:25])=[O:23])=[C:20]2[C:15]([CH:16]3[CH2:26][CH:17]3[CH2:18][O:19]2)=[CH:14][CH:13]=1)[S:8]([C:5]1[CH:6]=[CH:7][C:2]([F:1])=[CH:3][C:4]=1[N+:27]([O-:29])=[O:28])(=[O:10])=[O:9])=[O:34]

Participants

6

Reactant 4

HCID 6586Methyl chloroformateHCID 24758Sodium hydrideHCID 516892Sodium BicarbonateHCID 86713325methyl (1aRS,7bSR)-5-(4-fluoro-2-nitrobenzenesulfonylamino)-1,1a,2,7b-tetrahydrocyclopropa[c]chromene-4-carboxylate2×

Product 1

HCID 86713324methyl (1aRS,7bSR)-5-[N-(methoxycarbonyl)-N-(4-fluoro-2-nitrobenzene-sulfonyl)amino]-1,1a,2,7b-tetrahydro-cyclopropa[c]chromene-4-carboxylateYield 70.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of methyl (1aRS,7bSR)-5-(4-fluoro-2-nitrobenzenesulfonylamino)-1,1a,2,7b-tetrahydro-cyclopropa[c]chromene-4-carboxylate (Intermediate 112, 0.25 g) in THF (10 mL) was added dropwise with stirring to a cooled suspension of sodium hydride (0.1 g) in THF (5 mL) at 0° C. On completion of the addition, the mixture was stirred at room temperature for 30 minutes. Methyl chloroformate (0.3 g) was added dropwise and the mixture was stirred at room temperature for 1.5 hours. Saturated aqueous sodium bicarbonate was added and the mixture was extracted with ethyl acetate, dried (Na2SO4) and filtered. The filtrate was evaporated to dryness and the residue was purified by chromatography on silica, eluting with a mixture of ethyl acetate and petroleum ether to give methyl (1aRS,7bSR)-5-[N-(methoxycarbonyl)-N-(4-fluoro-2-nitrobenzenesulfonyl)amino]-1,1a,2,7b-tetrahydrocyclopropa-[c]chromene-4-carboxylate (0.2 g) as a white solid.

Workup

  1. additionOn completion of the addition
  2. stirringthe mixture was stirred at room temperature for 1.5 hours
  3. extractionthe mixture was extracted with ethyl acetate
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. customThe filtrate was evaporated to dryness
  7. customthe residue was purified by chromatography on silica
  8. washeluting with a mixture of ethyl acetate and petroleum ether

Sources & evidence

ORD record
ord-9d28778eca134915be809a63d91763c3
Source dataset
uspto-grants-2016_03
Patent number
US09290472B2

Reaction notes

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