Hydrochloric Acid → HCID 53357878, compound

HRID 1807294Notes

Reaction equation

HRID 1807294 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:32]=[CH:33][C:34]3[O:38][C:37]([C:39]([O:41]C)=[O:40])=[N:36][C:35]=3[CH:43]=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:32]=[CH:33][C:34]3[O:38][C:37]([C:39]([OH:41])=[O:40])=[N:36][C:35]=3[CH:43]=2)=[O:29])[CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 168937Lithium hydroxide, monohydrateHCID 53357877HCID 53357877, compound

Product 1

HCID 53357878HCID 53357878, compoundYield 12.4%

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)benzo[d]oxazole-2-carboxylate (64.5 mg, 0.101 mμmol) in THF (5 ml) was reacted with LITHIUM HYDROXIDE MONOHYDRATE (17.1 mg, 0.407 mmol) in water (2.5 ml) and stirred at rt for 4.5 hrs. The reaction mixture was treated with 1 N HCl (pH 5-6) and extracted with ethyl acetate. The organic extracts were washed with water, brine, dried with sodium sulfate, filtered and purified by silica gel chromatography with methylene chloride and methanol to give chiral-5-((2R,3S,4R,5S)-3-(3-chloro-2-fluorophenyl)-4-(4-chloro-2-fluorophenyl)-4-cyano-5-neopentylpyrrolidine-2-carboxamido)benzo[d]oxazole-2-carboxylic acid (7.8 mg., 12.4%) a white lyophilized solid. MS (ES+) m/z Calcd: [(M+H)+]: 627.13. found: 627.2. and chiral (2R,3S,4R,5S)—N-(benzo[d]oxazol-5-yl)-3-(3-chloro-2-fluorophenyl)-4-(4-chloro-2-fluorophenyl)-4-cyano-5-neopentylpyrrolidine-2-carboxamide (38.3 mg., 65.3%) as a white lyophilized solid. MS (ES+) m/z Calcd: [(M+H)+]: 583.14. found: 583.2.

Workup

  1. extractionextracted with ethyl acetate
  2. washThe organic extracts were washed with water, brine
  3. dry with materialdried with sodium sulfate
  4. filtrationfiltered
  5. custompurified by silica gel chromatography with methylene chloride and methanol

Sources & evidence

ORD record
ord-8f90efb32282443498aa17db900d2289
Source dataset
uspto-grants-2013_01
Patent number
US08354444B2

Reaction notes

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