Lithium Hydroxide → Hydrochloric Acid

HRID 2206422Notes

Reaction equation

HRID 2206422 reaction equation
[ClH:1].C[O:3][C:4](=[O:54])[C@H:5]([NH:12][C:13](=[O:53])[C:14]1[CH:19]=[CH:18][C:17]([NH:20][C:21]([C@H:23]2[C@H:27]([C:28]3[CH:33]=[CH:32][CH:31]=[C:30]([Cl:34])[C:29]=3[F:35])[C@:26]([C:38]3[CH:43]=[CH:42][C:41]([Cl:44])=[CH:40][C:39]=3[F:45])([C:36]#[N:37])[C@H:25]([CH2:46][C:47]([CH3:50])([CH3:49])[CH3:48])[NH:24]2)=[O:22])=[C:16]([O:51][CH3:52])[CH:15]=1)[CH2:6][CH2:7][C:8]([O:10]C)=[O:9].[OH-].[Li+]>O1CCCC1.O>[ClH:34].[Cl:44][C:41]1[CH:42]=[CH:43][C:38]([C@@:26]2([C:36]#[N:37])[C@H:25]([CH2:46][C:47]([CH3:49])([CH3:48])[CH3:50])[NH:24][C@@H:23]([C:21]([NH:20][C:17]3[CH:18]=[CH:19][C:14]([C:13]([NH:12][C@H:5]([CH2:6][CH2:7][C:8]([OH:10])=[O:9])[C:4]([OH:54])=[O:3])=[O:53])=[CH:15][C:16]=3[O:51][CH3:52])=[O:22])[C@@H:27]2[C:28]2[CH:33]=[CH:32][CH:31]=[C:30]([Cl:34])[C:29]=2[F:35])=[C:39]([F:45])[CH:40]=1.[ClH:1]

Participants

5

Reactant 2

HCID 3939Lithium HydroxideHCID 72547683HCID 72547683, compound

Product 2

HCID 313Hydrochloric AcidHCID 72547685HCID 72547685, compound

Reagents, catalysts & solvents 1

HCID 21881883Oxolane--water (1/1)Solvent

Procedure

(R)-2-(4-{[(2R,3S,4R,5S)-4-(4-Chloro-2-fluoro-phenyl)-3-(3-chloro-2-fluoro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carbonyl]-amino}-3-methoxy-benzoylamino)-pentanedioic acid dimethyl ester, hydrochloride (200 mg, 259 μmol) was suspended in 5 mL of tetrahydrofuran/water (4/1 ratio) then lithium hydroxide (100 mg) was added. After stirring at room temperature for 4 h, the reaction mixture was filtered, and the crude residue was purified by high-performance liquid chromatography (C18, eluting with 40-95% acetonitrile-water) to give (R)-2-(4-{[(2R,3S,4R,5S)-4-(4-chloro-2-fluoro-phenyl)-3-(3-chloro-2-fluoro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carbonyl]-amino}-3-methoxy-benzoylamino)-pentanedioic acid, hydrochloride after lyophilization with acetonitrile and 1N solution of hydrochloric acid. MS (ES+) m/z calcd. for C36H37Cl2F2N4O7: [(M+H)+]745. found: 745.

Workup

  1. filtrationthe reaction mixture was filtered
  2. customthe crude residue was purified by high-performance liquid chromatography (C18, eluting with 40-95% acetonitrile-water)

Sources & evidence

ORD record
ord-38bad4733075432e853e6e3236345f45
Source dataset
uspto-grants-2016_06
Patent number
US09371280B2

Reaction notes

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