Hydrochloric Acid → HCID 178444592, compound

HRID 1807287Notes

Reaction equation

HRID 1807287 reaction equation
[Cl:1][C:2]1[C:3]([F:44])=[C:4]([C@@H:8]2[C@:12]([C:15]3[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][C:16]=3[F:22])([C:13]#[N:14])[C@H:11]([CH2:23][C:24]([CH3:27])([CH3:26])[CH3:25])[NH:10][C@H:9]2[C:28]([NH:30][C:31]2[CH:43]=[CH:42][C:34]3[NH:35][C:36]([C:38]([O:40]C)=[O:39])=[N:37][C:33]=3[CH:32]=2)=[O:29])[CH:5]=[CH:6][CH:7]=1.O.[OH-].[Li+].Cl>C1COCC1.O>[Cl:1][C:2]1[C:3]([F:44])=[C:4]([C@@H:8]2[C@:12]([C:15]3[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][C:16]=3[F:22])([C:13]#[N:14])[C@H:11]([CH2:23][C:24]([CH3:27])([CH3:25])[CH3:26])[NH:10][C@H:9]2[C:28]([NH:30][C:31]2[CH:43]=[CH:42][C:34]3[NH:35][C:36]([C:38]([OH:40])=[O:39])=[N:37][C:33]=3[CH:32]=2)=[O:29])[CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 168937Lithium hydroxide, monohydrateHCID 178499041HCID 178499041, compound

Product 1

HCID 178444592HCID 178444592, compoundYield 43.6%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of chiral methyl 5-((2R,3S,4R,5S)-3-(3-chloro-2-fluorophenyl)-4-(4-chloro-2-fluorophenyl)-4-cyano-5-neopentylpyrrolidine-2-carboxamido)-1H-benzo[d]imidazole-2-carboxylate (84.4 mg, mmol) in THF (6 ml) was reacted with LITHIUM HYDROXIDE MONOHYDRATE (22.9 mg, 0.545 mmol) in water (3 ml) and stirred at rt overnight. The reaction mixture was treated with 1 N HCl (0.37 ml, pH 3-4) and extracted with ethyl acetate. The organic extract was washed with water and brine, dried with sodium sulfate, filtered and lyophilized to give chiral-5-((2R,3S,4R,5S)-3-(3-chloro-2-fluorophenyl)-4-(4-chloro-2-fluorophenyl)-4-cyano-5-neopentylpyrrolidine-2-carboxamido)-1H-benzo[d]imidazole-2-carboxylic acid (36 mg, 43.6%) a white solid, MS (ES+) m/z Calcd: [(M+H)+]: 626.15. found: 626.0.

Workup

  1. extractionextracted with ethyl acetate
  2. extractionThe organic extract
  3. washwas washed with water and brine
  4. dry with materialdried with sodium sulfate
  5. filtrationfiltered

Sources & evidence

ORD record
ord-f1e2f7c1fcc543ddb0b2be68b41631ca
Source dataset
uspto-grants-2013_01
Patent number
US08354444B2

Reaction notes

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