Trifluoroacetic acid → methyl (1aR,7bS)-5-[2-((S)-1-ethylpyrrolidin-3-yloxymethyl)-4-fluorobenzene-sulfonylamino]-1,1a,2,7b-tetrahydrocyclopropa[c]chromene-4-carboxylate

HRID 928068Notes

Reaction equation

HRID 928068 reaction equation
[F:1][C:2]1[CH:3]=[CH:4][C:5]([S:22](=[O:40])(=[O:39])[NH:23][C:24]2[CH:25]=[CH:26][C:27]3[C@H:28]4[CH2:38][C@H:29]4[CH2:30][O:31][C:32]=3[C:33]=2[C:34]([O:36][CH3:37])=[O:35])=[C:6]([CH:21]=1)[CH2:7][O:8][C@H:9]1[CH2:13][CH2:12][N:11](C(OC(C)(C)C)=O)[CH2:10]1.F[C:42](F)(F)[C:43](O)=O>C(Cl)Cl>[CH2:42]([C@H:7]([O:8][CH:9]1[CH2:13][CH2:12][NH:11][CH2:10]1)[C:6]1[CH:21]=[C:2]([F:1])[CH:3]=[CH:4][C:5]=1[S:22]([NH:23][C:24]1[C:33]([C:34]([O:36][CH3:37])=[O:35])=[C:32]2[C:27]([C@H:28]3[CH2:38][C@H:29]3[CH2:30][O:31]2)=[CH:26][CH:25]=1)(=[O:40])=[O:39])[CH3:43]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 71007006tert-butyl (S)-3-[(1aR,7bS)-5-fluoro-2-(4-methoxycarbonyl-1,1a,2,7b-tetrahydro-cyclopropa[c]chromen-5-ylsulfamoyl)benzyloxy]pyrrolidine-1-carboxylate2×

Product 1

HCID 86713274methyl (1aR,7bS)-5-[2-((S)-1-ethylpyrrolidin-3-yloxymethyl)-4-fluorobenzene-sulfonylamino]-1,1a,2,7b-tetrahydrocyclopropa[c]chromene-4-carboxylate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of tert-butyl (S)-3-[(1aR,7bS)-5-fluoro-2-(4-methoxycarbonyl-1,1a,2,7b-tetrahydro-cyclopropa[c]chromen-5-ylsulfamoyl)benzyloxy]pyrrolidine-1-carboxylate (Intermediate 214, 0.284 g) in trifluoroacetic acid (4 mL) and DCM (4 mL) was left at room temperature for 30 minutes. The mixture was evaporated in vacuo and the residue was azeotroped with toluene. The residue was dissolved in DCM (4 mL) and acetaldehyde (0.044 g) was added followed by sodium triacetoxyborohydride (0.212 g). The mixture was stirred at room temperature for 1 hour. The resulting solution was diluted with DCM and 1M sodium hydroxide solution and the organic layer was dried (Na2SO4) and filtered. The filtrate was evaporated in vacuo and the residue was purified by chromatography on silica, eluting with a mixture of methanol and DCM with a gradient of 0-20% to give methyl (1aR,7bS)-5-[2-((S)-1-ethylpyrrolidin-3-yloxymethyl)-4-fluorobenzenesulfonylamino]-1,1a,2,7b-tetrahydrocyclopropa[c]chromene-4-carboxylate (0.221 g) as a white foam.

Workup

  1. customThe mixture was evaporated in vacuo
  2. customthe residue was azeotroped with toluene
  3. dissolutionThe residue was dissolved in DCM (4 mL)
  4. additionacetaldehyde (0.044 g) was added
  5. additionThe resulting solution was diluted with DCM and 1M sodium hydroxide solution
  6. dry with materialthe organic layer was dried (Na2SO4)
  7. filtrationfiltered
  8. customThe filtrate was evaporated in vacuo
  9. customthe residue was purified by chromatography on silica
  10. washeluting with a mixture of methanol and DCM with a gradient of 0-20%

Sources & evidence

ORD record
ord-1872b0f7a4074f2f9618ff5bca4a3eb9
Source dataset
uspto-grants-2016_03
Patent number
US09290472B2

Reaction notes

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