Lithium Hydroxide → (R)-1-(3-(N-(1-carboxyethyl)-4-((5-(2-(4-chloro-3-methoxyphenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-Imidazol-2-ylthio)methyl)-3,5-difluorophenylsulfonamido)propyl)-4-aza-1-azoniabicyclo[2.2.2]octane chloride

HRID 83849Notes

Reaction equation

HRID 83849 reaction equation
[Br-].[Cl:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]([C:12]2[N:16]([C:17]3[CH:22]=[CH:21][C:20]([F:23])=[CH:19][CH:18]=3)[C:15]([S:24][CH2:25][C:26]3[C:31]([F:32])=[CH:30][C:29]([S:33]([N:36]([CH2:43][CH2:44][CH2:45][N+:46]45[CH2:53][CH2:52][N:49]([CH2:50][CH2:51]4)[CH2:48][CH2:47]5)[C@H:37]([CH3:42])[C:38]([O:40]C)=[O:39])(=[O:35])=[O:34])=[CH:28][C:27]=3[F:54])=[N:14][CH:13]=2)([CH3:11])[CH3:10])=[CH:5][C:4]=1[O:55][CH3:56].[Li+].[OH-]>CC#N>[Cl-:2].[C:38]([C@H:37]([N:36]([CH2:43][CH2:44][CH2:45][N+:46]12[CH2:47][CH2:48][N:49]([CH2:50][CH2:51]1)[CH2:52][CH2:53]2)[S:33]([C:29]1[CH:28]=[C:27]([F:54])[C:26]([CH2:25][S:24][C:15]2[N:16]([C:17]3[CH:18]=[CH:19][C:20]([F:23])=[CH:21][CH:22]=3)[C:12]([C:9]([C:6]3[CH:7]=[CH:8][C:3]([Cl:2])=[C:4]([O:55][CH3:56])[CH:5]=3)([CH3:10])[CH3:11])=[CH:13][N:14]=2)=[C:31]([F:32])[CH:30]=1)(=[O:34])=[O:35])[CH3:42])([OH:40])=[O:39]

Participants

4

Reactant 2

HCID 3939Lithium HydroxideHCID 86702239(R)-1-(3-(4-((5-(2-(4-chloro-3-methoxyphenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazol-2-ylthio)methyl)-3,5-difluoro-N-(1-methoxy-1-oxopropan-2-yl)phenylsulfonamido)propyl)-4-aza-1-azoniabicyclo[2.2.2]octane bromide

Product 1

HCID 67236512(R)-1-(3-(N-(1-carboxyethyl)-4-((5-(2-(4-chloro-3-methoxyphenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-Imidazol-2-ylthio)methyl)-3,5-difluorophenylsulfonamido)propyl)-4-aza-1-azoniabicyclo[2.2.2]octane chlorideYield 71%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a solution of (R)-1-(3-(4-((5-(2-(4-chloro-3-methoxyphenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazol-2-ylthio)methyl)-3,5-difluoro-N-(1-methoxy-1-oxopropan-2-yl)phenylsulfonamido)propyl)-4-aza-1-azoniabicyclo[2.2.2]octane bromide (118 mg, 0.14 mol) in MeCN (2 mL) was added 1N LiOH (0.3 mL). After stirring 1.5 h, the volatiles were removed under educed pressure. The resulting aqueous layer was acidified to pH 0 with 1N HCl and washed with EtOAc (2×10 mL). After extractions, the aqueous layer was neutralized to pH 7 with 1N NaOH and satd NaHCO3, and extracted with DCM/IPA (2:1, v/v, 3×10 mL). The combined extracts were dried (MgSO4), filtered and concentrated under reduced pressure. The residue was triturated in DCM, slurried with Celite and filtered over a pad of Celite to remove any inorganic salts. The DCM layer was concentrated and the residue recrystallized from DCM/Et2O (1:3) to give the title compound (83 mg, 71%) as a white solid.

Workup

  1. customthe volatiles were removed under educed pressure
  2. washwashed with EtOAc (2×10 mL)
  3. extractionAfter extractions
  4. extractionextracted with DCM/IPA (2:1, v/v, 3×10 mL)
  5. dry with materialThe combined extracts were dried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was triturated in DCM
  9. filtrationfiltered over a pad of Celite
  10. customto remove any inorganic salts
  11. concentrationThe DCM layer was concentrated
  12. customthe residue recrystallized from DCM/Et2O (1:3)

Sources & evidence

ORD record
ord-85cac81d22d14809b190c935bd7582ea
Source dataset
uspto-grants-2014_09
Patent number
US08846739B2

Reaction notes

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