Acetic Acid → HCID 130473163, compound

HRID 2279954Notes

Reaction equation

HRID 2279954 reaction equation
[Cl:1][C:2]1[CH:3]=[N+:4]([O-:49])[CH:5]=[C:6]([Cl:48])[C:7]=1[CH2:8][C@H:9]([O:20][C:21]([C:23]1[S:24][C:25]([CH2:28][NH:29][CH:30]([C:42]2[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=2)[C:31](=[O:41])[O:32][C@@H:33]2[CH:38]3[CH2:39][CH2:40][N:35]([CH2:36][CH2:37]3)[CH2:34]2)=[CH:26][CH:27]=1)=[O:22])[C:10]1[CH:15]=[CH:14][C:13]([O:16][CH3:17])=[C:12]([O:18][CH3:19])[CH:11]=1.[CH:50](=O)[CH3:51].C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(O)C(F)(F)F>[Cl:1][C:2]1[CH:3]=[N+:4]([O-:49])[CH:5]=[C:6]([Cl:48])[C:7]=1[CH2:8][C@H:9]([O:20][C:21]([C:23]1[S:24][C:25]([CH2:28][N:29]([CH2:50][CH3:51])[CH:30]([C:42]2[CH:43]=[CH:44][CH:45]=[CH:46][CH:47]=2)[C:31](=[O:41])[O:32][C@@H:33]2[CH:38]3[CH2:37][CH2:36][N:35]([CH2:40][CH2:39]3)[CH2:34]2)=[CH:26][CH:27]=1)=[O:22])[C:10]1[CH:15]=[CH:14][C:13]([O:16][CH3:17])=[C:12]([O:18][CH3:19])[CH:11]=1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 177AcetaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 118117140HCID 118117140, compound

Product 1

HCID 130473163HCID 130473163, compoundYield 25.4%

Reagents, catalysts & solvents 1

HCID 64092,2,2-TrifluoroethanolSolvent

Conditions

Temperature
40 °C

Procedure

A suspension of [(1S)-2-(3,5-dichloro-1-oxido-pyridin-1-ium-4-yl)-1-(3,4-dimethoxyphenyl)ethyl]5-[[[2-oxo-1-phenyl-2-[(3R)-quinuclidin-3-yl]oxy-ethyl]amino]methyl]thiophene-2-carboxylate (Example 42, 100 mg, 0.12 mmol) in trifluoroethanol (0.5 mL) was heated at 40 C for 5 min. Acetaldehyde (11 μL, 0.19 mmol) was added followed by acetic acid (7 μL, 0.12 mmol) and the reaction mixture was heated at 40° C. for 18 h. Sodium triacetoxyborohydride (52 mg, 0.25 mmol) was added and the mixture was heated at 40° C. for 2 h. The solvent was evaporated in vacuo and the residue was partitioned between ethyl acetate (1 mL) and water (1 mL). 0.2N aqueous HCl was added to adjust pH=1. The acidic aqueous phase was washed with ethyl acetate (3×1 mL), sodium chloride (1 g) was added to the aqueous phase that was extracted with chloroform (3×1 mL), the combined chloroform extracts were filtered through a phase separator and the solvent was removed in vacuo. The combined ethyl acetate washes were extracted with 0.2N HCl (1 mL), water (1 mL). The aqueous phases were combined, saturated with solid sodium chloride and extracted with chloroform (3×1 mL). The crude product from both extractions was combined and purification by preparative HPLC gave the title compound as an off-white solid (23 mg, 24%).

Workup

  1. temperaturewas heated at 40 C for 5 min
  2. temperaturethe mixture was heated at 40° C. for 2 h
  3. customThe solvent was evaporated in vacuo
  4. customthe residue was partitioned between ethyl acetate (1 mL) and water (1 mL)
  5. addition0.2N aqueous HCl was added
  6. washThe acidic aqueous phase was washed with ethyl acetate (3×1 mL), sodium chloride (1 g)
  7. additionwas added to the aqueous phase that
  8. extractionwas extracted with chloroform (3×1 mL)
  9. filtrationthe combined chloroform extracts were filtered through a phase separator
  10. customthe solvent was removed in vacuo
  11. extractionThe combined ethyl acetate washes were extracted with 0.2N HCl (1 mL), water (1 mL)
  12. extractionextracted with chloroform (3×1 mL)
  13. extractionThe crude product from both extractions
  14. custompurification by preparative HPLC

Sources & evidence

ORD record
ord-d00a16a48d6348a0b36af1b72515374d
Source dataset
uspto-grants-2015_09
Patent number
US09133185B2

Reaction notes

Loading…