Trifluoroacetic acid → quinuclidin-4-yl 5-fluoro-1-(methylsulfonyl)-1H-indole-3-carboxylate 2,2,2-trifluoroacetic acid

HRID 624670Notes

Reaction equation

HRID 624670 reaction equation
[F:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([S:11]([CH3:14])(=[O:13])=[O:12])[CH:6]=[C:5]2[C:15]([OH:17])=[O:16].[F:18][C:19]([F:30])([F:29])[C:20]([O:22]C(=O)C(F)(F)F)=[O:21].C(O)(C(F)(F)F)=O.[N:38]12[CH2:45][CH2:44][C:41](O)([CH2:42][CH2:43]1)[CH2:40][CH2:39]2>C1(C)C=CC=CC=1>[F:18][C:19]([F:30])([F:29])[C:20]([OH:22])=[O:21].[F:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([S:11]([CH3:14])(=[O:13])=[O:12])[CH:6]=[C:5]2[C:15]([O:17][C:41]12[CH2:44][CH2:45][N:38]([CH2:43][CH2:42]1)[CH2:39][CH2:40]2)=[O:16]

Participants

6

Reactant 4

HCID 6422Trifluoroacetic acidHCID 9845Trifluoroacetic anhydrideHCID 1412901-Azabicyclo(2.2.2)octan-4-olHCID 900309845-Fluoro-1-(methylsulfonyl)-1H-indole-3-carboxylic acid

Product 1

HCID 90031208quinuclidin-4-yl 5-fluoro-1-(methylsulfonyl)-1H-indole-3-carboxylate 2,2,2-trifluoroacetic acid

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

In a vial containing 5-fluoro-1-(methylsulfonyl)-1H-indole-3-carboxylic acid (20 mg, 0.078 mmol; see Reference 10 for the synthesis) and trifluoroacetic anhydride (10.98 μl, 0.078 mmol) in toluene (259 μl) was added TFA (64.8 μl). After 30 min, quinuclidin-4-ol (8.24 mg, 0.065 mmol) was added and the mixture was stirred at RT overnight. Direct HPLC purification (after dilution with DMF and filtration) gave the title compound as a clear film. MS (ESI, pos. ion) m/z: 367.2 (M+1).

Workup

  1. filtrationDirect HPLC purification (after dilution with DMF and filtration)

Sources & evidence

ORD record
ord-b885b1d9b92d4236ac90212911fe267c
Source dataset
uspto-grants-2016_04
Patent number
US09303045B2

Reaction notes

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