Acetic Acid → HCID 118142792, compound

HRID 2279951Notes

Reaction equation

HRID 2279951 reaction equation
Cl.Cl.[NH2:3][CH:4]([C:16]1[CH:21]=[CH:20][CH:19]=[C:18]([F:22])[CH:17]=1)[C:5]([O:7][C@@H:8]1[CH:13]2[CH2:14][CH2:15][N:10]([CH2:11][CH2:12]2)[CH2:9]1)=[O:6].CCN(CC)CC.[Cl:30][C:31]1[CH:32]=[N+:33]([O-:60])[CH:34]=[C:35]([Cl:59])[C:36]=1[CH2:37][C@H:38]([O:49][C:50]([C:52]1[S:53][C:54]([CH:57]=O)=[CH:55][CH:56]=1)=[O:51])[C:39]1[CH:44]=[CH:43][C:42]([O:45][CH3:46])=[C:41]([O:47][CH3:48])[CH:40]=1.C(O)(=O)C.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>CCOC(C)=O>[Cl:59][C:35]1[CH:34]=[N+:33]([O-:60])[CH:32]=[C:31]([Cl:30])[C:36]=1[CH2:37][C@H:38]([O:49][C:50]([C:52]1[S:53][C:54]([CH2:57][NH:3][CH:4]([C:16]2[CH:21]=[CH:20][CH:19]=[C:18]([F:22])[CH:17]=2)[C:5](=[O:6])[O:7][C@@H:8]2[CH:13]3[CH2:12][CH2:11][N:10]([CH2:15][CH2:14]3)[CH2:9]2)=[CH:55][CH:56]=1)=[O:51])[C:39]1[CH:44]=[CH:43][C:42]([O:45][CH3:46])=[C:41]([O:47][CH3:48])[CH:40]=1

Participants

7

Reactant 5

HCID 176Acetic AcidHCID 8471TriethylamineHCID 5049666Sodium triacetoxyborohydrideHCID 118142901HCID 118142901, compoundHCID 131733497HCID 131733497, compound

Product 1

HCID 118142792HCID 118142792, compoundYield 59%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

A suspension of (R)-quinuclidin-3-yl 2-amino-2-(3-fluorophenyl)acetate bis hydrochloride salt (0.176 g, 0.500 mmol) in EtOAc (5 mL) was added with Et3N (0.150 mL, 1.10 mmol). The reaction mixture was stirred at room temperature for 2 h. The precipitate obtained was filtered, washed with EtOAc (˜5 mL) and the solvent was removed in vacuo. This residue was dissolved in CH3CN (5 mL) and to the solution was added [(1S)-2-(3,5-dichloro-1-oxido-pyridin-1-ium-4-yl)-1-(3,4-dimethoxyphenyl)ethyl]5-formylthiophene-2-carboxylate (0.220 g, 0.456 mmol) followed by acetic acid (0.026 mL, 0.456 mmol). The reaction mixture was stirred at room temperature for 20 h. NaBH(OAc)3 (0.265 g, 1.25 mmol) was added and the reaction mixture was stirred at room temperature for a further 24 h. The excess solvent was removed in vacuo and the residue was partitioned between EtOAc (30 mL) and saturated aqueous NaHCO3 solution (20 mL). The organic layer was washed with saturated brine (2×15 mL), separated and filtered through a phase separator cartridge and the solvent was removed in vacuo. Purification by preparative HPLC gave the title compound (1:1 mixture of diastereoisomers) as a pale yellow solid (200 mg, 59%).

Workup

  1. customThe precipitate obtained
  2. filtrationwas filtered
  3. washwashed with EtOAc (˜5 mL)
  4. customthe solvent was removed in vacuo
  5. dissolutionThis residue was dissolved in CH3CN (5 mL) and to the solution
  6. stirringThe reaction mixture was stirred at room temperature for 20 h
  7. stirringthe reaction mixture was stirred at room temperature for a further 24 h
  8. customThe excess solvent was removed in vacuo
  9. customthe residue was partitioned between EtOAc (30 mL) and saturated aqueous NaHCO3 solution (20 mL)
  10. washThe organic layer was washed with saturated brine (2×15 mL)
  11. customseparated
  12. filtrationfiltered through a phase separator cartridge
  13. customthe solvent was removed in vacuo
  14. customPurification by preparative HPLC

Sources & evidence

ORD record
ord-71b87ff888ae410d817587479320a5c1
Source dataset
uspto-grants-2015_09
Patent number
US09133185B2

Reaction notes

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