Lithium Hydroxide → HCID 53357617, compound

HRID 1807327Notes

Reaction equation

HRID 1807327 reaction equation
C[O:2][C:3](=[O:44])[C:4]([C:7]1[CH:12]=[CH:11][C:10]([NH:13][C:14]([C@H:16]2[C@H:20]([C:21]3[CH:26]=[CH:25][CH:24]=[C:23]([Cl:27])[C:22]=3[F:28])[C@:19]([C:31]3[CH:36]=[CH:35][C:34]([Cl:37])=[CH:33][C:32]=3[F:38])([C:29]#[N:30])[C@H:18]([CH2:39][C:40]([CH3:43])([CH3:42])[CH3:41])[NH:17]2)=[O:15])=[CH:9][CH:8]=1)([CH3:6])[CH3:5].[Li+].[OH-]>C1COCC1.CO.O>[Cl:27][C:23]1[C:22]([F:28])=[C:21]([C@@H:20]2[C@:19]([C:31]3[CH:36]=[CH:35][C:34]([Cl:37])=[CH:33][C:32]=3[F:38])([C:29]#[N:30])[C@H:18]([CH2:39][C:40]([CH3:43])([CH3:42])[CH3:41])[NH:17][C@H:16]2[C:14]([NH:13][C:10]2[CH:9]=[CH:8][C:7]([C:4]([CH3:6])([CH3:5])[C:3]([OH:44])=[O:2])=[CH:12][CH:11]=2)=[O:15])[CH:26]=[CH:25][CH:24]=1

Participants

6

Reactant 2

HCID 3939Lithium HydroxideHCID 58046942HCID 58046942, compound

Product 1

HCID 53357617HCID 53357617, compoundYield 58.4%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

A mixture of chiral 2-(4-{[(2R,3S,4R,5S)-3-(3-chloro-2-fluoro-phenyl)-4-(4-chloro-2-fluoro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carbonyl]-amino}-phenyl)-2-methyl-propionic acid methyl ester (21 mg, 0.0327 mmol) was dissolved in THF (3 mL) and methanol (1 mL), followed by 2N LiOH (1 mL). The reaction mixture was stirred at room temperature for 14 hours. The mixture was diluted with water and extracted with ethyl acetate (2×). The organic phase was separated then concentrated under reduced pressure to afford crude product. The compound was purified by RP-HPLC (30%-95% of acetonitrile/water) to afford of chiral 2-(4-{[(2R,3S,4R,5S)-3-(3-chloro-2-fluoro-phenyl)-4-(4-chloro-2-fluoro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carbonyl]-amino}-phenyl)-2-methyl-propionic acid (12 mg, 58.4%) as an off-white solid. HRMS (ES+) m/z Calcd for C33H33Cl2F2N3O3+H [(M+H)+]: 628.1940. found: 628.1937.

Workup

  1. extractionextracted with ethyl acetate (2×)
  2. customThe organic phase was separated
  3. concentrationthen concentrated under reduced pressure
  4. customto afford crude product
  5. customThe compound was purified by RP-HPLC (30%-95% of acetonitrile/water)

Sources & evidence

ORD record
ord-b569c7f1661b4e8185015e8aade943b2
Source dataset
uspto-grants-2013_01
Patent number
US08354444B2

Reaction notes

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