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

HRID 2284840Notes

Reaction equation

HRID 2284840 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 (I13, 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, prepared as previously reported for Int 6, Step 6). The reaction was stirred at 0° C. for 1 hour and then allowed to warm to RT for 16 h. Water was added to the reaction mixture and the mixture was extracted with ethyl acetate (×3). The combined extracts were washed with brine, dried over sodium sulfate, filtered and the solvent was removed in vacuo. 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. customprepared
  2. temperatureto warm to RT for 16 h
  3. extractionthe mixture was extracted with ethyl acetate (×3)
  4. washThe combined extracts were washed with brine
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. customthe solvent was removed in vacuo
  8. customThe crude material was purified by chromatography on a KP-NH Biotage cartridge
  9. washeluting with 0-20% methanol in ethyl acetate

Sources & evidence

ORD record
ord-73040a70b8de4c52a36158f7c4e06e85
Source dataset
uspto-grants-2015_09
Patent number
US09145409B2

Reaction notes

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