Dichloromethane → HCID 86713354, compound

HRID 928050Notes

Reaction equation

HRID 928050 reaction equation
[F:1][C:2]1[CH:3]=[CH:4][C:5]([S:21](=[O:39])(=[O:38])[NH:22][C:23]2[CH:24]=[CH:25][C:26]3[CH:27]4[CH2:37][CH:28]4[CH2:29][O:30][C:31]=3[C:32]=2[C:33]([O:35][CH3:36])=[O:34])=[C:6]([CH2:8][CH2:9][CH:10]2[CH2:13][N:12]([C:14](OC(C)(C)C)=O)[CH2:11]2)[CH:7]=1.[CH2:40](Cl)Cl>FC(F)(F)C(O)=O>[CH2:14]([N:12]1[CH2:13][CH:10]([CH2:9][CH2:8][C:6]2[CH:7]=[C:2]([F:1])[CH:3]=[CH:4][C:5]=2[S:21]([NH:22][C:23]2[C:32]([C:33]([O:35][CH3:36])=[O:34])=[C:31]3[C:26]([CH:27]4[CH2:37][CH:28]4[CH2:29][O:30]3)=[CH:25][CH:24]=2)(=[O:39])=[O:38])[CH2:11]1)[CH3:40]

Participants

4

Reactant 2

HCID 6344DichloromethaneHCID 86713355HCID 86713355, compound2×

Product 1

HCID 86713354HCID 86713354, compound

Reagents, catalysts & solvents 1

HCID 6422Trifluoroacetic acidSolvent

Procedure

A solution of tert-butyl (1aRS,7bSR)-3-{2-[5-fluoro-2-(4-methoxycarbonyl-1,1a,2,7b-tetrahydrocyclopropa[c]chromen-5-ylsulfamoyl)phenyl]ethyl}azetidine-1-carboxylate (Intermediate 184, 0.397 g) in DCM (5 mL) and trifluoroacetic acid (5 mL) was left at room temperature for 30 minutes then evaporated in vacuo and the residue was dissolved in toluene and re-evaporated. The residue was dissolved in DCM (15 mL) and acetaldehyde (0.063 g) was added followed by sodium triacetoxyborohydride (0.301 g). The mixture was stirred at room temperature for 2 hours then diluted with ethyl acetate and water and the organic layer was dried (Na2SO4) and filtered. The filtrate was concentrated in vacuo and the residue was purified by chromatography on silica, eluting with a mixture of methanol and DCM with a gradient of 0-25% to give methyl (1aRS,7bSR)-5-{2-[2-(1-ethylazetidin-3-yl)ethyl]-4-fluorobenzenesulfonylamino}-1,1a,2,7b-tetrahydrocyclopropa[c]chromene-4-carboxylate (0.312 g) as a white foam.

Workup

  1. customthen evaporated in vacuo
  2. dissolutionthe residue was dissolved in toluene
  3. customre-evaporated
  4. dissolutionThe residue was dissolved in DCM (15 mL)
  5. additionacetaldehyde (0.063 g) was added
  6. additionthen diluted with ethyl acetate and water
  7. dry with materialthe organic layer was dried (Na2SO4)
  8. filtrationfiltered
  9. concentrationThe filtrate was concentrated in vacuo
  10. customthe residue was purified by chromatography on silica
  11. washeluting with a mixture of methanol and DCM with a gradient of 0-25%

Sources & evidence

ORD record
ord-285b1ad6aefd4e6787e6919c73f2c9b1
Source dataset
uspto-grants-2016_03
Patent number
US09290472B2

Reaction notes

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