Ammonium Chloride → (S)-4-[2-(3-fluoro-2-methyl-benzyl)-1-phenyl-indolizine-3-carbonyl]-2-(2-hydroxy-ethyl)-piperazine-1-carboxylic acid tert-butyl ester

HRID 1963062Notes

Reaction equation

HRID 1963062 reaction equation
[F-].C([N+](CCCC)(CCCC)CCCC)CCC.[C:19]([O:23][C:24]([N:26]1[CH2:31][CH2:30][N:29]([C:32]([C:34]2[N:42]3[C:37]([CH:38]=[CH:39][CH:40]=[CH:41]3)=[C:36]([C:43]3[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=3)[C:35]=2[CH2:49][C:50]2[CH:55]=[CH:54][CH:53]=[C:52]([F:56])[C:51]=2[CH3:57])=[O:33])[CH2:28][C@@H:27]1[CH2:58][CH2:59][O:60][Si](C(C)(C)C)(C)C)=[O:25])([CH3:22])([CH3:21])[CH3:20].[Cl-].[NH4+]>C1COCC1>[C:19]([O:23][C:24]([N:26]1[CH2:31][CH2:30][N:29]([C:32]([C:34]2[N:42]3[C:37]([CH:38]=[CH:39][CH:40]=[CH:41]3)=[C:36]([C:43]3[CH:44]=[CH:45][CH:46]=[CH:47][CH:48]=3)[C:35]=2[CH2:49][C:50]2[CH:55]=[CH:54][CH:53]=[C:52]([F:56])[C:51]=2[CH3:57])=[O:33])[CH2:28][C@@H:27]1[CH2:58][CH2:59][OH:60])=[O:25])([CH3:21])([CH3:22])[CH3:20]

Participants

5

Reactant 3

HCID 25517Ammonium ChlorideHCID 2724141Tetrabutylammonium FluorideHCID 70663954(S)-2-[2-(tert-Butyl-dimethyl-silyloxy)-ethyl]-4-[2-(3-fluoro-2-methyl-benzyl)-1-phenyl-indolizine-3-carbonyl]-piperazine-1-carboxylic acid tert-butyl ester

Product 1

HCID 67773585(S)-4-[2-(3-fluoro-2-methyl-benzyl)-1-phenyl-indolizine-3-carbonyl]-2-(2-hydroxy-ethyl)-piperazine-1-carboxylic acid tert-butyl esterYield 99.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

A 1 M solution of tetrabutylammonium fluoride in THF (2.82 ml, 2.82 mmol) was added to a solution of the compound of step 4 (1.29 g, 1.88 mmol) in 7.5 ml of THF cooled to 0° C. under argon. The mixture was stirred at room temperature for 2 h and then 100 ml of a saturated solution of ammonium chloride were added. The solution was extracted twice with 50 ml each of EA, and the combined organic phases were washed with brine, dried over sodium sulfate, filtered and evaporated to dryness under reduced pressure. The residue was purified by chromatography on silica gel (DCM/MOH, 100:0, then 98:2) to give 1.069 g of the title compound as an off-white powder melting at 85° C.

Workup

  1. extractionThe solution was extracted twice with 50 ml each of EA
  2. washthe combined organic phases were washed with brine
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. customevaporated to dryness under reduced pressure
  6. customThe residue was purified by chromatography on silica gel (DCM/MOH, 100:0

Sources & evidence

ORD record
ord-2562e691a6674ee0a0d064a80268ed9a
Source dataset
uspto-grants-2013_04
Patent number
US08415336B2

Reaction notes

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