(3R)-1-azabicyclo[2.2.2]octan-3-yl carbonochloridate hydrochloride → [(1S)-1-[3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl]-2-(3,5-dichloro-1-oxido-pyridin-1-ium-4-yl)ethyl]2-hydroxy-3-[(2-hydroxy-N-[(3R)-quinuclidin-3-yl]oxycarbonyl-anilino)methyl]benzoate formate

HRID 1497997Notes

Reaction equation

HRID 1497997 reaction equation
[CH:1]1([CH2:4][O:5][C:6]2[CH:7]=[C:8]([C@@H:16]([O:27][C:28](=[O:45])[C:29]3[CH:34]=[CH:33][CH:32]=[C:31]([CH2:35][NH:36][C:37]4[CH:42]=[CH:41][CH:40]=[CH:39][C:38]=4[OH:43])[C:30]=3[OH:44])[CH2:17][C:18]3[C:23]([Cl:24])=[CH:22][N+:21]([O-:25])=[CH:20][C:19]=3[Cl:26])[CH:9]=[CH:10][C:11]=2[O:12][CH:13]([F:15])[F:14])[CH2:3][CH2:2]1.Cl.[C:47](Cl)(=[O:57])[O:48][C@@H:49]1[CH:54]2[CH2:55][CH2:56][N:51]([CH2:52][CH2:53]2)[CH2:50]1>CC#N>[CH:28]([OH:45])=[O:27].[CH:1]1([CH2:4][O:5][C:6]2[CH:7]=[C:8]([C@@H:16]([O:27][C:28](=[O:45])[C:29]3[CH:34]=[CH:33][CH:32]=[C:31]([CH2:35][N:36]([C:47]([O:48][C@@H:49]4[CH:54]5[CH2:55][CH2:56][N:51]([CH2:52][CH2:53]5)[CH2:50]4)=[O:57])[C:37]4[CH:42]=[CH:41][CH:40]=[CH:39][C:38]=4[OH:43])[C:30]=3[OH:44])[CH2:17][C:18]3[C:23]([Cl:24])=[CH:22][N+:21]([O-:25])=[CH:20][C:19]=3[Cl:26])[CH:9]=[CH:10][C:11]=2[O:12][CH:13]([F:14])[F:15])[CH2:2][CH2:3]1

Participants

4

Reactant 2

HCID 86676896(3R)-1-azabicyclo[2.2.2]octan-3-yl carbonochloridate hydrochlorideHCID 86720718[(1S)-1-[3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl]-2-(3,5-dichloro-1-oxido-pyridin-1-ium-4-yl)ethyl]2-hydroxy-3-[(2-hydroxyanilino)-methyl]benzoate

Product 1

HCID 86720719[(1S)-1-[3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl]-2-(3,5-dichloro-1-oxido-pyridin-1-ium-4-yl)ethyl]2-hydroxy-3-[(2-hydroxy-N-[(3R)-quinuclidin-3-yl]oxycarbonyl-anilino)methyl]benzoate formateYield 79.5%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A solution of [(1S)-1-[3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl]-2-(3,5-dichloro-1-oxido-pyridin-1-ium-4-yl)ethyl]2-hydroxy-3-[(2-hydroxyanilino)-methyl]benzoate (250 mg, 0.38 mmol) in CH3CN (6 mL) was added (R)-quinuclidin-3-yl carbonochloridate hydrochloride (150 mg, 0.66 mmol) in one portion. The resulting slurry was stirred at room temperature for 1 hour and concentrated in vacuo. The residue was purified by preparative HPLC to provide the title compound as a pale yellow solid (130 mg, 42%).

Workup

  1. concentrationconcentrated in vacuo
  2. customThe residue was purified by preparative HPLC

Sources & evidence

ORD record
ord-5f3c13158111401b9d4ce5fdba646095
Source dataset
uspto-grants-2015_12
Patent number
US09199980B2

Reaction notes

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