Triacetoxyperiodinane → HCID 130473170, compound

HRID 2279960Notes

Reaction equation

HRID 2279960 reaction equation
[Cl:1][C:2]1[CH:3]=[N+:4]([O-:33])[CH:5]=[C:6]([Cl:32])[C:7]=1[CH2:8][C@H:9]([O:20][C:21](=[O:31])[CH2:22][C:23]1[S:24][C:25]([CH2:28][CH2:29][OH:30])=[CH:26][CH:27]=1)[C:10]1[CH:15]=[CH:14][C:13]([O:16][CH3:17])=[C:12]([O:18][CH3:19])[CH:11]=1.CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C=CC=CC1=2)=O>ClCCl>[Cl:32][C:6]1[CH:5]=[N+:4]([O-:33])[CH:3]=[C:2]([Cl:1])[C:7]=1[CH2:8][C@H:9]([O:20][C:21](=[O:31])[CH2:22][C:23]1[S:24][C:25]([CH2:28][CH:29]=[O:30])=[CH:26][CH:27]=1)[C:10]1[CH:15]=[CH:14][C:13]([O:16][CH3:17])=[C:12]([O:18][CH3:19])[CH:11]=1

Participants

4

Reactant 2

HCID 159087TriacetoxyperiodinaneHCID 130473177HCID 130473177, compound

Product 1

HCID 130473170HCID 130473170, compoundYield 94%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of [(1S)-2-(3,5-dichloro-1-oxido-pyridin-1-ium-4-yl)-1-(3,4-dimethoxyphenyl)ethyl]2-[5-(2-hydroxyethyl)-2-thienyl]acetate (80 mg, 0.16 mmol) in dichloromethane (2 mL) at −78° C. was added Dess-Martin periodinane (81 mg, 0.19 mmol). The reaction solution was stirred at room temperature for 30 minutes. The reaction solution was washed with saturated aqueous sodium thiosulfate (5 mL) followed by saturated aqueous sodium bicarbonate (5 mL). The organic phase was passed through a hydrophobic fit and concentrated in vacuo to give [(1S)-2-(3,5-dichloro-1-oxido-pyridin-1-ium-4-yl)-1-(3,4-dimethoxyphenyl)ethyl]2-[5-(2-oxoethyl)-2-thienyl]acetate as a brown solid (76 mg, 94%) which was used in the next step without further purification. To a solution of the crude residue (199 mg, 0.39 mmol) in ethanol (20 mL) was added [(3R)-quinuclidin-3-yl]2-amino-2-phenyl-acetate hydrochloride salt (260 mg, 0.78 mmol), triethylamine (219 μL, 1.56 mmol) and acetic acid (102 μL, 0.78 mmol). The resultant solution was stirred at room temperature for 20 minutes. Sodium borohydride (49 mg, 0.78 mmol) was then added and the resultant solution was stirred at room temperature for 18 h. The solvent was removed in vacuo and the residue taken up in water (20 mL) and ethyl acetate (20 mL). The layers were separated and the aqueous phase was extracted with ethyl acetate (2×20 mL). The combined organic phases were extracted with 0.2 N aqueous hydrochloric acid (40 mL) and water (40 mL). The aqueous extracts were combined and sodium chloride (6 g) was added. The mixture was extracted with chloroform (3×30 mL) and the combined organic extracts were passed through a hydrophobic fit and the solvent was removed in vacuo. Purification of the crude material by preparative HPLC afforded the title compound (42 mg, 14%) as an off-white solid.

Workup

  1. washThe reaction solution was washed with saturated aqueous sodium thiosulfate (5 mL)
  2. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-13c5edaf787f45beb3ba8bada9a235bb
Source dataset
uspto-grants-2015_09
Patent number
US09133185B2

Reaction notes

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