Trifluoroacetic acid → 4-{(2S)-3-[7-(2-Aminoethyl)-9-oxa-3,7-diazabicyclo[3.3.1]non-3-yl]-2-hydroxypropoxy}benzonitrile

HRID 1992332Notes

Reaction equation

HRID 1992332 reaction equation
[C:1]([C:3]1[CH:32]=[CH:31][C:6]([O:7][CH2:8][C@@H:9]([OH:30])[CH2:10][N:11]2[CH2:18][CH:17]3[O:19][CH:13]([CH2:14][N:15]([CH2:20][CH2:21][NH:22]C(=O)OC(C)(C)C)[CH2:16]3)[CH2:12]2)=[CH:5][CH:4]=1)#[N:2].FC(F)(F)C(O)=O.C([O-])([O-])=O.[K+].[K+]>C(Cl)Cl>[NH2:22][CH2:21][CH2:20][N:15]1[CH2:16][CH:17]2[O:19][CH:13]([CH2:12][N:11]([CH2:10][C@H:9]([OH:30])[CH2:8][O:7][C:6]3[CH:5]=[CH:4][C:3]([C:1]#[N:2])=[CH:32][CH:31]=3)[CH2:18]2)[CH2:14]1

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 11430Potassium CarbonateHCID 9876235Azd 7009

Product 1

HCID 685227854-{(2S)-3-[7-(2-Aminoethyl)-9-oxa-3,7-diazabicyclo[3.3.1]non-3-yl]-2-hydroxypropoxy}benzonitrileYield 70.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

tert-Butyl 2-{7-[(2S)-3-(4-cyanophenoxy)-2-hydroxypropyl]-9-oxa-3,7-di-azabicyclo[3.3.1]non-3-yl}ethylcarbamate (2.9 g, 6.56 mmol; see WO 01/28992) was dissolved in DCM (30 mL). Trifluoroacetic acid (22.2 g, 194.7 mmol) was added and the solution was stirred for 2 h. The mixture was concentrated under reduced pressure, redissolved in toluene and acetonitrile and concentrated in vacuo again. The product mixture was dissolved in acetonitrile (50 mL) and solid K2CO3 (9.7 g, 10.2 mmol) was added. The mixture was filtered and concentrated under reduced pressure. The mixture was then redissolved in a mixture of EtOAc and a saturated solution of NaHCO3. The mixture was extracted twice with DCM, the combined organic extracts dried (Na2SO4) and evaporated to afford 1.6 g (68.7%) of the title compound.

Workup

  1. concentrationThe mixture was concentrated under reduced pressure
  2. dissolutionredissolved in toluene
  3. concentrationacetonitrile and concentrated in vacuo again
  4. dissolutionThe product mixture was dissolved in acetonitrile (50 mL)
  5. filtrationThe mixture was filtered
  6. concentrationconcentrated under reduced pressure
  7. dissolutionThe mixture was then redissolved in a mixture of EtOAc
  8. extractionThe mixture was extracted twice with DCM
  9. dry with materialthe combined organic extracts dried (Na2SO4)
  10. customevaporated

Sources & evidence

ORD record
ord-164213ce8bdf45d7915dff0fcae0f6ce
Source dataset
uspto-grants-2010_01
Patent number
US07648985B2

Reaction notes

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