Trifluoroacetic acid → HCID 118114112, compound

HRID 2284848Notes

Reaction equation

HRID 2284848 reaction equation
C([O:5][C:6]([NH:8][C@@H:9]([C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1)[C:10]1[CH:11]=[C:12]([CH:33]=[CH:34][CH:35]=1)[O:13][CH2:14][C:15]1[CH:20]=[CH:19][C:18]([S:21]([N:24]2[CH2:28][CH2:27][CH2:26][C@H:25]2[C:29]([O:31][CH3:32])=[O:30])(=[O:23])=[O:22])=[CH:17][CH:16]=1)=[O:7])(C)(C)C.C(O)(C(F)(F)F)=O.Cl.C(Cl)(=O)O[C@@H:52]1[CH:57]2[CH2:58][CH2:59][N:54]([CH2:55][CH2:56]2)[CH2:53]1>C(Cl)Cl.CCOC(C)=O.O>[C:36]1([C@H:9]([NH:8][C:6]([O:5][C@@H:52]2[CH:57]3[CH2:58][CH2:59][N:54]([CH2:55][CH2:56]3)[CH2:53]2)=[O:7])[C:10]2[CH:11]=[C:12]([CH:33]=[CH:34][CH:35]=2)[O:13][CH2:14][C:15]2[CH:16]=[CH:17][C:18]([S:21]([N:24]3[CH2:28][CH2:27][CH2:26][C@H:25]3[C:29]([O:31][CH3:32])=[O:30])(=[O:22])=[O:23])=[CH:19][CH:20]=2)[CH:37]=[CH:38][CH:39]=[CH:40][CH:41]=1

Participants

7

Reactant 3

HCID 6422Trifluoroacetic acidHCID 86676896(3R)-1-azabicyclo[2.2.2]octan-3-yl carbonochloridate hydrochlorideHCID 118114421HCID 118114421, compound

Product 1

HCID 118114112HCID 118114112, compoundYield 197.6%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a mixture of (S)-methyl 1-((4-((3-((S)-((tert-butoxycarbonyl)amino)(phenyl)-methyl)-phenoxy)methyl)phenyl)-sulfonyl)pyrrolidine-2-carboxylate (I28, 636 mg, 1.1 mmol) in DCM (10 mL) was added TFA (3 mL) at 0° C. The reaction mixture was warmed to room temperature and stirred for 30 min before being concentrated in vacuo. The residue was diluted in DCM (50 mL) and washed with saturated aqueous NaHCO3 (50 mL). The organic phase was passed through a hydrophobic frit and solvent was removed in vacuo. The residue (436 mg) was dissolved in pyridine (4 mL) and the reaction mixture was cooled to 0° C. (R)-quinuclidin-3-yl carbonochloridate hydrochloride (207 mg, 0.92 mmol, prepared as previously reported in 16, step 6) was added and the resulting mixture was stirred at room temperature for 16 h. Additional (R)-quinuclidin-3-yl carbonochloridate hydrochloride (104 mg, 0.46 mmol) was added at 0° C., the mixture was stirred for 2 h and then diluted with EtOAc (50 mL) and water (20 mL). The layers were separated and organic phase dried over MgSO4. The mixture was filtered and the solvent was removed in vacuo to yield 576 mg of the crude title product as a thick oil which was used in the next step without further purification.

Workup

  1. concentrationbefore being concentrated in vacuo
  2. additionThe residue was diluted in DCM (50 mL)
  3. washwashed with saturated aqueous NaHCO3 (50 mL)
  4. customwas removed in vacuo
  5. dissolutionThe residue (436 mg) was dissolved in pyridine (4 mL)
  6. temperaturethe reaction mixture was cooled to 0° C. (R)-quinuclidin-3-yl carbonochloridate hydrochloride (207 mg, 0.92 mmol
  7. customprepared
  8. additionwas added
  9. stirringthe resulting mixture was stirred at room temperature for 16 h
  10. stirringthe mixture was stirred for 2 h
  11. customThe layers were separated
  12. dry with materialorganic phase dried over MgSO4
  13. filtrationThe mixture was filtered
  14. customthe solvent was removed in vacuo

Sources & evidence

ORD record
ord-f2b8b22946af4a139c83dd801000ba04
Source dataset
uspto-grants-2015_09
Patent number
US09145409B2

Reaction notes

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