Hydrochloric Acid → HCID 53236399, compound

HRID 417275Notes

Reaction equation

HRID 417275 reaction equation
C[O:2][C:3](=[O:43])[C:4]1[CH:9]=[CH:8][C:7]([NH:10][C:11]([C@@H:13]2[NH:17][C@@H:16]([CH2:18][C:19]([CH3:22])([CH3:21])[CH3:20])[C@:15]3([C:30]4[C:25](=[CH:26][C:27]([Cl:31])=[CH:28][CH:29]=4)[NH:24][C:23]3=[O:32])[C@H:14]2[C:33]2[CH:38]=[CH:37][CH:36]=[C:35]([Br:39])[C:34]=2[F:40])=[O:12])=[C:6]([O:41][CH3:42])[CH:5]=1.[OH-].[Na+].Cl>CO.C1COCC1.O>[Br:39][C:35]1[C:34]([F:40])=[C:33]([C@H:14]2[C@H:13]([C:11]([NH:10][C:7]3[CH:8]=[CH:9][C:4]([C:3]([OH:43])=[O:2])=[CH:5][C:6]=3[O:41][CH3:42])=[O:12])[NH:17][C@@H:16]([CH2:18][C:19]([CH3:22])([CH3:21])[CH3:20])[C@@:15]32[C:30]2[C:25](=[CH:26][C:27]([Cl:31])=[CH:28][CH:29]=2)[NH:24][C:23]3=[O:32])[CH:38]=[CH:37][CH:36]=1

Participants

7

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 53236398HCID 53236398, compound

Product 1

HCID 53236399HCID 53236399, compound

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of rac-4-{[(2′S,3′R,4′S,5′R)-4′-(3-bromo-2-fluoro-phenyl)-6-chloro-2′-(2,2-dimethyl-propyl)-2-oxo-1,2-dihydro-spiro[indole-3,3′-pyrrolidine]-5′-carbonyl]amino}-3-methoxy-benzoic acid methyl ester (0.2 g, 0.3 mmol) in MeOH (3 mL) and THF (9 mL) was added an aqueous solution (1N) of NaOH (6 mL, 6 mmol). The reaction mixture was stirred at room temperature for 18 h. The crude mixture was diluted with water (5 mL), and acidified to “pH” 5-6 by dilute aqueous HCl solution. The mixture was then extracted with ethyl acetate three times. The combined organic extract was washed with water, brine, dried over MgSO4, and concentrated. The residue was triturated with dichlormethane and hexanes to give rac-4-{[(2′S,3′R,4′S,5′R)-4′-(3-bromo-2-fluoro-phenyl)-6-chloro-2′-(2,2-dimethyl-propyl)-2-oxo-1,2-dihydro-spiro[indole-3,3′-pyrrolidine]-5′-carbonyl]-amino}-3-methoxy-benzoic acid as a white powder (Yield, 0.16 g, 82%).

Workup

  1. extractionThe mixture was then extracted with ethyl acetate three times
  2. extractionThe combined organic extract
  3. washwas washed with water, brine
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated
  6. customThe residue was triturated with dichlormethane and hexanes
  7. customto give

Sources & evidence

ORD record
ord-aff6959cf1474d34a112253a3971a97f
Source dataset
uspto-grants-2012_01
Patent number
US08088815B2

Reaction notes

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