Water → methyl 4-((3-((S)-phenyl((((R)-quinuclidin-3-yloxy)carbonyl)amino)methyl)phenoxy)methyl)benzoate

HRID 2205712Notes

Reaction equation

HRID 2205712 reaction equation
Cl.[NH2:2][C@@H:3]([C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)[C:4]1[CH:5]=[C:6]([CH:19]=[CH:20][CH:21]=1)[O:7][CH2:8][C:9]1[CH:18]=[CH:17][C:12]([C:13]([O:15][CH3:16])=[O:14])=[CH:11][CH:10]=1.[C:28](Cl)(=[O:38])[O:29][C@@H:30]1[CH:35]2[CH2:36][CH2:37][N:32]([CH2:33][CH2:34]2)[CH2:31]1.O>N1C=CC=CC=1>[C:22]1([C@H:3]([NH:2][C:28]([O:29][C@@H:30]2[CH:35]3[CH2:36][CH2:37][N:32]([CH2:33][CH2:34]3)[CH2:31]2)=[O:38])[C:4]2[CH:5]=[C:6]([CH:19]=[CH:20][CH:21]=2)[O:7][CH2:8][C:9]2[CH:18]=[CH:17][C:12]([C:13]([O:15][CH3:16])=[O:14])=[CH:11][CH:10]=2)[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=1

Participants

5

Reactant 3

HCID 962WaterHCID 20812191(R)-quinuclidin-3-yl carbonochloridateHCID 86720812(S)-Methyl 4-((3-(amino(phenyl)methyl)phenoxy)methyl)benzoate hydrochloride

Product 1

HCID 86720814methyl 4-((3-((S)-phenyl((((R)-quinuclidin-3-yloxy)carbonyl)amino)methyl)phenoxy)methyl)benzoateYield 66%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Conditions

Temperature
0 °C

Procedure

To a stirred solution of (S)-methyl 4-((3-(amino(phenyl)methyl)phenoxy)-methyl)benzoate hydrochloride (12.0 g, 31.3 mmol) in pyridine (100 mL) at 0° C. was added portion-wise (R)-quinuclidin-3-yl carbonochloridate (8.50 g, 37.5 mmol). The reaction was stirred at 0° C. for 1 hour and then allowed to warm to RT for 16 hours. Water was added to the reaction mixture and extracted with ethyl acetate (×3). The combined extracts were washed with brine, dried (sodium sulfate), filtered and the solvent evaporated at reduced pressure. The crude material was purified by chromatography on a KP-NH Biotage cartridge eluting with 0-20% methanol in ethyl acetate to afford the title compound (10.3 g, 66%).

Workup

  1. temperatureto warm to RT for 16 hours
  2. extractionextracted with ethyl acetate (×3)
  3. washThe combined extracts were washed with brine
  4. dry with materialdried (sodium sulfate)
  5. filtrationfiltered
  6. customthe solvent evaporated at reduced pressure
  7. customThe crude material was purified by chromatography on a KP-NH Biotage cartridge
  8. washeluting with 0-20% methanol in ethyl acetate

Sources & evidence

ORD record
ord-0c75402a9873417681029daa3ac83058
Source dataset
uspto-grants-2016_06
Patent number
US09371318B2

Reaction notes

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