Hydrochloric Acid → HCID 67296997, compound

HRID 1807031Notes

Reaction equation

HRID 1807031 reaction equation
C[O:2][C:3]([CH:5]1[CH:9]([C:10]2[CH:15]=[CH:14][CH:13]=[C:12]([Cl:16])[C:11]=2[F:17])[C:8]([C:20]2[CH:25]=[CH:24][C:23]([Cl:26])=[CH:22][C:21]=2[F:27])([C:18]#[N:19])[CH:7]([CH2:28][C:29]([CH3:40])([CH3:39])[CH2:30][C:31]2[CH:36]=[CH:35][C:34]([O:37][CH3:38])=[CH:33][CH:32]=2)[NH:6]1)=[O:4].[OH-].[Na+].CO.Cl>O1CCCC1>[Cl:16][C:12]1[C:11]([F:17])=[C:10]([CH:9]2[C:8]([C:20]3[CH:25]=[CH:24][C:23]([Cl:26])=[CH:22][C:21]=3[F:27])([C:18]#[N:19])[CH:7]([CH2:28][C:29]([CH3:40])([CH3:39])[CH2:30][C:31]3[CH:32]=[CH:33][C:34]([O:37][CH3:38])=[CH:35][CH:36]=3)[NH:6][CH:5]2[C:3]([OH:4])=[O:2])[CH:15]=[CH:14][CH:13]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 887MethanolHCID 14798Sodium HydroxideHCID 67297089HCID 67297089, compound

Product 1

HCID 67296997HCID 67296997, compoundYield 102.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To rac-(2R,3S,4R,5S)-3-(3-chloro-2-fluoro-phenyl)-4-(4-chloro-2-fluoro-phenyl)-4-cyano-5-[3-(4-methoxy-phenyl)-2,2-dimethyl-propyl]-pyrrolidine-2-carboxylic acid methyl ester prepared in Example 126b (4 g, 6.8 mmol) in tetrahydrofuran (60 mL) was added an aqueous solution (1 N) of NaOH (20 mL, 20 mmol) and methanol (20 mL). The reaction mixture was stirred at room temperature for 3 h. The “pH” of the mixture was adjusted to ˜4-5 by aqueous HCl solution. The mixture was concentrated. The residue was partitioned between ethyl acetate and water. The organic layer was separated, washed with water, brine, dried over MgSO4, concentrated to give rac-(2R,3S,4R,5S)-3-(3-chloro-2-fluoro-phenyl)-4-(4-chloro-2-fluoro-phenyl)-4-cyano-5-[3-(4-methoxy-phenyl)-2,2-dimethyl-propyl]-pyrrolidine-2-carboxylic acid as a light yellow solid (4 g, 100%)

Workup

  1. concentrationThe mixture was concentrated
  2. customThe residue was partitioned between ethyl acetate and water
  3. customThe organic layer was separated
  4. washwashed with water, brine
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-05c83873d6e849aca7f4b74b4f839fa3
Source dataset
uspto-grants-2013_01
Patent number
US08354444B2

Reaction notes

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