Lithium Hydroxide → HCID 86642693, compound

HRID 1807307Notes

Reaction equation

HRID 1807307 reaction equation
[F:1][C:2]([F:7])([F:6])[C:3]([OH:5])=[O:4].C[O:9][C:10](=[O:49])[C@@H:11]([NH:18][C:19]([C@H:21]1[C@H:25]([C:26]2[CH:31]=[CH:30][CH:29]=[C:28]([Cl:32])[C:27]=2[F:33])[C@:24]([C:36]2[CH:41]=[CH:40][C:39]([Cl:42])=[CH:38][C:37]=2[F:43])([C:34]#[N:35])[C@H:23]([CH2:44][C:45]([CH3:48])([CH3:47])[CH3:46])[NH:22]1)=[O:20])[CH2:12][C:13]1[N:14]=[CH:15][S:16][CH:17]=1.[Li+].[OH-]>C1COCC1.CO.O>[F:1][C:2]([F:7])([F:6])[C:3]([OH:5])=[O:4].[Cl:32][C:28]1[C:27]([F:33])=[C:26]([C@@H:25]2[C@:24]([C:36]3[CH:41]=[CH:40][C:39]([Cl:42])=[CH:38][C:37]=3[F:43])([C:34]#[N:35])[C@H:23]([CH2:44][C:45]([CH3:48])([CH3:47])[CH3:46])[NH:22][C@H:21]2[C:19]([NH:18][C@@H:11]([CH2:12][C:13]2[N:14]=[CH:15][S:16][CH:17]=2)[C:10]([OH:49])=[O:9])=[O:20])[CH:31]=[CH:30][CH:29]=1

Participants

6

Reactant 2

HCID 3939Lithium HydroxideHCID 86642694HCID 86642694, compound

Product 1

HCID 86642693HCID 86642693, compoundYield 37.9%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

A mixture of chiral (S)-2-{[(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}-3-thiazol-4-yl-propionic acid methyl ester trifluoroacetate salt (112 mg, 0.176 mmol) was dissolved in THF (3 mL) and methanol (1 mL), then 2N LiOH (1 mL) was added and stirred at room temperature for 2 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 the crude product that was purified by RP-HPLC (20-95% acetonitrile/water). The solvent was evaporated under reduced pressure to afford chiral (S)-2-{[(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}-3-thiazol-4-yl-propionic acid trifluoroacetate salt as a white powder (41 mg, 37.9%). HRMS (ES+) m/z Calcd for C29H28Cl2F2N4O3S+H [(M+H)+]: 621.1300. found: 621.1298.

Workup

  1. extractionextracted with ethyl acetate (2×)
  2. customthe organic phase was separated
  3. concentrationthen concentrated under reduced pressure
  4. customto afford the crude product that
  5. customwas purified by RP-HPLC (20-95% acetonitrile/water)
  6. customThe solvent was evaporated under reduced pressure

Sources & evidence

ORD record
ord-4f1dd8a0b7a349979be2b4b5f23f2709
Source dataset
uspto-grants-2013_01
Patent number
US08354444B2

Reaction notes

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