Bicyclo[2.2.1]heptane-1-methanesulfonic acid, 7,7-dimethyl-2-oxo-, (1S)- → HCID 178506131, compound

HRID 1518114Notes

Reaction equation

HRID 1518114 reaction equation
[NH2:1][C:2]1[C:7]([C:8]([F:11])([F:10])[F:9])=[CH:6][C:5]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=2[C:18]([F:21])([F:20])[F:19])=[CH:4][C:3]=1[NH:22][C:23]([C:25]1[CH2:29][C:28]2([CH2:34][CH2:33][CH2:32][CH2:31][CH2:30]2)[O:27][N:26]=1)=O.CC1(C)C2(CS(O)(=O)=O)C(CC1CC2)=O>O1CCOCC1>[F:11][C:8]([F:9])([F:10])[C:7]1[C:2]2[NH:1][C:23]([C:25]3[CH2:29][C:28]4([CH2:30][CH2:31][CH2:32][CH2:33][CH2:34]4)[O:27][N:26]=3)=[N:22][C:3]=2[CH:4]=[C:5]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=2[C:18]([F:19])([F:21])[F:20])[CH:6]=1

Participants

4

Reactant 2

HCID 18462Bicyclo[2.2.1]heptane-1-methanesulfonic acid, 7,7-dimethyl-2-oxo-, (1S)-HCID 59280104HCID 59280104, compound

Product 1

HCID 178506131HCID 178506131, compoundYield 91%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

1-Oxa-2-aza-spiro[4.5]dec-2-ene-3-carboxylic acid (4-amino-5,2′-bis-trifluoromethyl-biphenyl-3-yl)-amide (9.22 g, 19.0 mmol, as prepared in the previous step) was placed in a 250 mL round-bottom flask equipped with a magnetic stir bar. Dry dioxane (200 mL) and CSA (883 mg, 3.80 mmol) were added. The flask was fitted with a reflux condenser, and the mixture was stirred at 100° C. for 7.5 h. The reaction was cooled to RT, and the solvent was removed under reduced pressure. The residue was dissolved in EtOAc (100 mL) and washed twice with satd aq NaHCO3 (50 mL). The organic extract was dried over MgSO4, filtered, and the solvent was removed under reduced pressure. The residue was dissolved in a minimum amount of MeOH (50 mL) and placed in a freezer for 1 h. The resulting precipitate was isolated by filtration and washed with MeOH. The precipitate was purified by recrystallization from hot MeOH (30 mL), giving a pale yellow solid, which was dried under high vacuum. The filtrate was concentrated under reduced pressure and purified by column chromatography using an 80-g SiO2 pre-packed column eluting with EtOAc/hexanes, 0:1 to 3:7, v/v over 30 min. The solid precipitate and column-purified material were combined, yielding 8.12 g (91%) of the title compound. 1H-NMR (400 MHz, CDCl3) 6: 1H-NMR (400 MHz, DMSO-d6) δ: 7.89 (d, J=7.6 Hz, 1H), 7.77 (t, J=7.3 Hz, 1H), 7.68 (t, J=7.6 Hz, 2H), 7.55 (d, J=7.6 Hz, 1H), 7.48 (s, 1H), 3.33 (s, 2H), 1.63-1.82 (m, 6H), 1.35-1.58 (m, 4H).

Workup

  1. customwas placed in a 250 mL round-bottom flask
  2. customequipped with a magnetic stir bar
  3. customThe flask was fitted with a reflux condenser
  4. temperatureThe reaction was cooled to RT
  5. customthe solvent was removed under reduced pressure
  6. dissolutionThe residue was dissolved in EtOAc (100 mL)
  7. washwashed twice with satd aq NaHCO3 (50 mL)
  8. extractionThe organic extract
  9. dry with materialwas dried over MgSO4
  10. filtrationfiltered
  11. customthe solvent was removed under reduced pressure
  12. dissolutionThe residue was dissolved in a minimum amount of MeOH (50 mL)
  13. waitplaced in a freezer for 1 h
  14. customThe resulting precipitate was isolated by filtration
  15. washwashed with MeOH
  16. customThe precipitate was purified by recrystallization from hot MeOH (30 mL)
  17. customgiving a pale yellow solid, which
  18. customwas dried under high vacuum
  19. concentrationThe filtrate was concentrated under reduced pressure
  20. custompurified by column chromatography
  21. washeluting with EtOAc/hexanes, 0:1 to 3:7, v/v over 30 min
  22. customThe solid precipitate and column-purified material

Sources & evidence

ORD record
ord-e4d50239dc344be9aaa6f11d14d4f76b
Source dataset
uspto-grants-2012_07
Patent number
US08232409B2

Reaction notes

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