HCID 86712106, compound → HCID 86712105, compound

HRID 715939Notes

Reaction equation

HRID 715939 reaction equation
[CH2:1]([N:3]([CH2:37][CH3:38])[CH2:4]/[CH:5]=[CH:6]\[C:7]1[CH:12]=[C:11]([F:13])[CH:10]=[CH:9][C:8]=1[S:14]([NH:17][C:18]1[CH:27]=[CH:26][C:25]2[N:24]3[CH2:28][CH2:29][C@@H:23]3[CH2:22][O:21][C:20]=2[C:19]=1[C:30]([O:32]C(C)(C)C)=[O:31])(=[O:16])=[O:15])[CH3:2]>C(O)(C(F)(F)F)=O.C(Cl)Cl>[CH2:37]([N:3]([CH2:1][CH3:2])[CH2:4]/[CH:5]=[CH:6]\[C:7]1[CH:12]=[C:11]([F:13])[CH:10]=[CH:9][C:8]=1[S:14]([NH:17][C:18]1[CH:27]=[CH:26][C:25]2[N:24]3[CH2:28][CH2:29][C@@H:23]3[CH2:22][O:21][C:20]=2[C:19]=1[C:30]([OH:32])=[O:31])(=[O:15])=[O:16])[CH3:38]

Participants

4

Reactant 1

HCID 86712106HCID 86712106, compound2×

Product 1

HCID 86712105HCID 86712105, compoundYield 52.5%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 6422Trifluoroacetic acidSolvent

Procedure

A solution of tert-butyl (R)-6-[2-((Z)-3-diethylaminoprop-1-enyl)-4-fluorobenzenesulfonyl-amino]-1,2,2a,3-tetrahydro-4-oxa-8b-azacyclobuta[a]naphthalene-5-carboxylate (Intermediate 42, 0.017 g) in TFA (2 mL) and DCM (2 mL) was left to stand at room temperature for 30 minutes then concentrated in vacuo. The residue was dissolved in methanol (15 mL) and potassium carbonate (0.2 g) was added and the mixture stirred for 5 minutes then filtered. The filtrate was acidified with formic acid and concentrated in vacuo. The residue was triturated with 20% methanol in DCM 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 0-20%. The resultant solid was triturated with diethyl ether and filtered to give (R)-6-[2-((Z)-3-diethylaminoprop-1-enyl)-4-fluorobenzenesulfonylamino]-1,2,2a,3-tetrahydro-4-oxa-8b-aza-cyclobuta[a]naphthalene-5-carboxylic acid (0.008 g) as a light brown solid.

Workup

  1. concentrationthen concentrated in vacuo
  2. dissolutionThe residue was dissolved in methanol (15 mL)
  3. additionpotassium carbonate (0.2 g) was added
  4. filtrationthen filtered
  5. concentrationconcentrated in vacuo
  6. customThe residue was triturated with 20% methanol in DCM
  7. filtrationfiltered
  8. concentrationThe filtrate was concentrated 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%
  11. customThe resultant solid was triturated with diethyl ether
  12. filtrationfiltered

Sources & evidence

ORD record
ord-024de26bc67a40cab1cd0349176e87a8
Source dataset
uspto-grants-2015_11
Patent number
US09187494B2

Reaction notes

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