Trifluoroacetic anhydride → HCID 66876350, compound

HRID 1019277Notes

Reaction equation

HRID 1019277 reaction equation
[BH4-].[Na+].[CH2:3]([N:10]1[C@H:15]2[CH2:16][CH2:17][C@@H:11]1[CH:12]([C:19]([O:21][CH3:22])=[O:20])[C:13](=O)[CH2:14]2)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.[Cl-].[NH4+].C(=O)([O-])O.[Na+].FC(F)(F)C(OC(=O)C(F)(F)F)=O>C(N(CC)CC)C.CN(C1C=CN=CC=1)C.CO>[CH2:3]([N:10]1[C@H:15]2[CH2:16][CH2:17][C@@H:11]1[C:12]([C:19]([O:21][CH3:22])=[O:20])=[CH:13][CH2:14]2)[C:4]1[CH:5]=[CH:6][CH:7]=[CH:8][CH:9]=1

Participants

9

Reactant 5

HCID 9845Trifluoroacetic anhydrideHCID 25517Ammonium ChlorideHCID 516892Sodium Bicarbonate2×HCID 4311764Sodium borohydrideHCID 66876149HCID 66876149, compound

Product 1

HCID 66876350HCID 66876350, compoundYield 81.2%

Reagents, catalysts & solvents 3

HCID 8471TriethylamineCatalystHCID 142844-(Dimethylamino)pyridineCatalystHCID 887MethanolSolvent

Procedure

Under a nitrogen atmosphere, NaBH4 (69.6 mg, 1.84 mmol) was added to a methanol (10 ml) solution of the methyl (1R,5S)-8-benzyl-3-oxo-8-azabicyclo[3.2.1]octane-2-carboxylate ((−)-2b) (264 mg, 0.92 mmol) obtained in Example 19, in an ice bath, and the reaction mixture was stirred for 2 hours. After completion of the reaction, a saturated aqueous ammonium chloride solution was added to the reaction mixture and the excess solvent was evapolated under reduced pressure. The residue was adjusted to pH 8.0-8.5 with a saturated aqueous sodium hydrogencarbonate solution and extracted with chloroform. The extract was dried over Na2SO4, filtered and then concentrated in vacuo. Then, the residue was dissolved in chloroform (10 ml) under a nitrogen atmosphere, and triethylamine (267 μl, 1.91 mmol) and DMAP as a catalyst were added thereto. In an ice bath, trifluoroacetic anhydride (203 μl, 1.44 mmol) was added thereto and the resulting mixture was stirred at room temperature for 44 hours. After completion of the reaction, the reaction mixture was adjusted to pH 8.0-8.5 with a saturated aqueous sodium hydrogencarbonate solution and extracted with chloroform. The extract was dried over Na2SO4, filtered and then concentrated in vacuo, and the thus obtained crude product was purified by a silica gel column chromatography (AcOEt:hexane=1:5) to obtain 192.2 mg of the title compound methyl (1R,5S)-8-benzyl-8-azabicyclo[3.2.1]octan-2-ene-2-carboxylate. The yield from the above two steps was 81 mol %.

Workup

  1. customAfter completion of the reaction
  2. extractionextracted with chloroform
  3. dry with materialThe extract was dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. dissolutionThen, the residue was dissolved in chloroform (10 ml) under a nitrogen atmosphere
  7. stirringthe resulting mixture was stirred at room temperature for 44 hours
  8. customAfter completion of the reaction
  9. extractionextracted with chloroform
  10. dry with materialThe extract was dried over Na2SO4
  11. filtrationfiltered
  12. concentrationconcentrated in vacuo
  13. customthe thus obtained crude product
  14. customwas purified by a silica gel column chromatography (AcOEt:hexane=1:5)

Sources & evidence

ORD record
ord-bbce144259ba4c0a8e049ce7b79a5d94
Source dataset
uspto-grants-2002_11
Patent number
US06486323B1

Reaction notes

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