Trifluoroacetic acid → HCID 68761279, compound

HRID 529103Notes

Reaction equation

HRID 529103 reaction equation
[CH2:1]([CH:8]1[CH2:13][C:12](=[CH:14]OC)[CH2:11][CH2:10][N:9]1[C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl.[Cl:25][C:26]1[CH:31]=[CH:30][C:29]([NH:32]N)=[CH:28][CH:27]=1.C(O)(C(F)(F)F)=O.C(N(CC)CC)C.CC(OC(OC(OC(C)(C)C)=O)=O)(C)C>C(Cl)(Cl)Cl.CCOC(C)=O>[CH2:1]([CH:8]1[CH2:13][C:12]2([C:30]3[C:29](=[CH:28][CH:27]=[C:26]([Cl:25])[CH:31]=3)[N:32]=[CH:14]2)[CH2:11][CH2:10][N:9]1[C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

8

Reactant 5

HCID 6422Trifluoroacetic acidHCID 8471TriethylamineHCID 71600Hydrazine, (4-chlorophenyl)-, hydrochloride (1:1)HCID 90495Di-tert-butyl dicarbonateHCID 68734285HCID 68734285, compound

Product 1

HCID 68761279HCID 68761279, compound

Reagents, catalysts & solvents 2

HCID 6212ChloroformSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

Tert-butyl 2-benzyl-4-(methoxymethylene)piperidine-1-carboxylate (274 mg, 0.86 mmol) and (4-chlorophenyl)hydrazine hydrochloride (186 mg, 1.04 mmol) were dissolved in chloroform (10 mL) and then TFA (1.0 mL, 12.98 mmol) was added. The resulting mixture was heated to reflux for 8 h at which time it was cooled to ambient and then quenched by the slow addition of saturated sodium bicarbonate solution. The reaction mixture was dissolved in EtOAc and then washed twice with water and once with brine. The organic portion was dried over magnesium sulfate, filtered and concentrated. The residue was dissolved in dichloromethane (10 mL) and cooled to 0° C. Triethylamine (0.24 mL, 1.73 mmol) was added followed by boc anhydride (189 mg, 0.86 mmol). The resulting solution was warmed ambient and stirred at this temperature for 12 h. At this time, it was taken up in EtOAc and washed twice with water and once with brine. The organic layer was dried over magnesium sulfate, filtered and concentrated. The residue thus obtained was purified via silica gel chromatography to give tert-butyl 2′-benzyl-5-chlorospiro[indole-3,4′-piperidine]-1′-carboxylate as a mixture of diastereomers (220 mg, 62%). LCMS (APCI+) m/z 411.1 [M+H]+; Rt=4.56, 4.63 min.

Workup

  1. temperatureThe resulting mixture was heated
  2. temperatureto reflux for 8 h at which time it
  3. temperaturewas cooled to ambient and
  4. customthen quenched by the slow addition of saturated sodium bicarbonate solution
  5. dissolutionThe reaction mixture was dissolved in EtOAc
  6. washwashed twice with water and once with brine
  7. dry with materialThe organic portion was dried over magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated
  10. dissolutionThe residue was dissolved in dichloromethane (10 mL)
  11. temperatureThe resulting solution was warmed ambient
  12. washwashed twice with water and once with brine
  13. dry with materialThe organic layer was dried over magnesium sulfate
  14. filtrationfiltered
  15. concentrationconcentrated
  16. customThe residue thus obtained
  17. customwas purified via silica gel chromatography

Sources & evidence

ORD record
ord-91286df9b6ea419a80dc83e5e26c9c24
Source dataset
uspto-grants-2016_05
Patent number
US09346805B2

Reaction notes

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