p-Toluenesulfonic acid monohydrate → (1S,5S)-3-(5,6-dichloro-3-pyridinyl)-3,6-diazabicyclo[3.2.0]heptane p-toluenesulfonate

HRID 495088Notes

Reaction equation

HRID 495088 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([N:9]2[CH2:15][C@@H:14]3[C@@H:11]([CH2:12][N:13]3C(OC(C)(C)C)=O)[CH2:10]2)[CH:5]=[N:6][C:7]=1[Cl:8].O.[C:24]1([CH3:34])[CH:29]=[CH:28][C:27]([S:30]([OH:33])(=[O:32])=[O:31])=[CH:26][CH:25]=1>C(OCC)(=O)C>[C:24]1([CH3:34])[CH:25]=[CH:26][C:27]([S:30]([OH:33])(=[O:31])=[O:32])=[CH:28][CH:29]=1.[Cl:1][C:2]1[CH:3]=[C:4]([N:9]2[CH2:15][C@@H:14]3[C@@H:11]([CH2:12][NH:13]3)[CH2:10]2)[CH:5]=[N:6][C:7]=1[Cl:8]

Participants

4

Reactant 2

HCID 521998p-Toluenesulfonic acid monohydrateHCID 23634672tert-butyl (1R,5S)-3-(5,6-dichloro-3-pyridinyl)-3,6-diazabicyclo[3.2.0]heptane-6-carboxylate

Product 1

HCID 11495356(1S,5S)-3-(5,6-dichloro-3-pyridinyl)-3,6-diazabicyclo[3.2.0]heptane p-toluenesulfonate

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

The product of Example 3A (23.2 g) was dissolved in ethyl acetate (250 mL) and p-toluenesulfonic acid monohydrate (11.4 g, 60 mmol) was added. The solution was warmed to reflux and stirred for 90 minutes, cooled to room temperature, and allowed to stand for 12 hours to complete precipitation. The solid was isolated by filtration and dried to provide the title compound. mp 174-178° C.; [α]D20=−20.0° (MeOH, 0.105); 1H NMR (MeOH-d4, 300 MHz) δ 2.36 (s, 3H), 3.06 (dd, J=10.5, 6.1 Hz, 1H), 3.17 (dd, J=12.2, 4.8 Hz, 1H), 3.50 (m, 1H), 3.72 (dd, J=11.2, 5.4 Hz, 1H), 3.90 (d, J=10.5 Hz, 1H), 4.10 (d, J=12.6 Hz, 1H), 4.25 (dd, J=11.2, 9.8 Hz, 1H), 5.05 (dd, J=6.7, 5.1 Hz, 1H) 7.22 (d, J=8.1 Hz, 2H), 7.52 (d, J=2.7 Hz, 1H), 7.69 (d, J=8.1 Hz, 2H), 7.95 (d, J=2.7 Hz, 1H); MS (DCI/NH3) m/z 244/246/248 (M+H)+.

Workup

  1. temperatureThe solution was warmed
  2. temperatureto reflux
  3. waitto stand for 12 hours
  4. customprecipitation
  5. customThe solid was isolated by filtration
  6. customdried

Sources & evidence

ORD record
ord-8a01e776a30d4f6687b754efb7da65d0
Source dataset
uspto-grants-2009_05
Patent number
US07538226B2

Reaction notes

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