Lithium Hydroxide → {(S)-1-tert-Butoxycarbonyl-4-[2-(3-fluoro-2-methyl-benzyl)-1-phenyl-indolizine-3-carbonyl]-piperazin-2-yl}-acetic acid

HRID 1963071Notes

Reaction equation

HRID 1963071 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]([C:16]2[N:24]3[C:19]([CH:20]=[CH:21][CH:22]=[CH:23]3)=[C:18]([C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)[C:17]=2[CH2:31][C:32]2[CH:37]=[CH:36][CH:35]=[C:34]([F:38])[C:33]=2[CH3:39])=[O:15])[CH2:10][C@@H:9]1[CH2:40][C:41]([O:43]C)=[O:42])=[O:7])([CH3:4])([CH3:3])[CH3:2].[OH-].[Li+]>O1CCOCC1>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]([C:16]2[N:24]3[C:19]([CH:20]=[CH:21][CH:22]=[CH:23]3)=[C:18]([C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)[C:17]=2[CH2:31][C:32]2[CH:37]=[CH:36][CH:35]=[C:34]([F:38])[C:33]=2[CH3:39])=[O:15])[CH2:10][C@@H:9]1[CH2:40][C:41]([OH:43])=[O:42])=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

4

Reactant 2

HCID 3939Lithium HydroxideHCID 67772153(S)-4-[2-(3-Fluoro-2-methyl-benzyl)-1-phenyl-indolizine-3-carbonyl]-2-methoxycarbonylmethyl-piperazine-1-carboxylic acid tert-butyl ester

Product 1

HCID 70663959{(S)-1-tert-Butoxycarbonyl-4-[2-(3-fluoro-2-methyl-benzyl)-1-phenyl-indolizine-3-carbonyl]-piperazin-2-yl}-acetic acidYield 100.4%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of the compound of step 4 (1.40 g, 2.33 mmol) in 15.5 ml of dioxane was added 3.5 ml of a 1 M aqueous solution of lithium hydroxide and the mixture was heated at 50° C. for 1 h. The solvents were evaporated under reduced pressure and the residue was dissolved in 45 ml of water. The solution was cooled to 0° C. and acidified to pH 2 with 5 N hydrochloric acid. The obtained suspension was extracted with EA and the combined organic phases were washed with brine, dried over sodium sulfate, filtered and evaporated to dryness. 1.37 g of the title compound were obtained as a green solid melting at 103-105° C.

Workup

  1. customThe solvents were evaporated under reduced pressure
  2. dissolutionthe residue was dissolved in 45 ml of water
  3. temperatureThe solution was cooled to 0° C.
  4. extractionThe obtained suspension was extracted with EA
  5. washthe combined organic phases were washed with brine
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. customevaporated to dryness

Sources & evidence

ORD record
ord-f8f47d30e0c441308698c1a957c8f282
Source dataset
uspto-grants-2013_04
Patent number
US08415336B2

Reaction notes

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