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 1963062ノート

反応式

HRID 1963062 の反応式
[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]

参加物

5

反応物 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

生成物 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 ester収率 99.5%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒2 回

反応条件

温度
0 °C

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-2562e691a6674ee0a0d064a80268ed9a
出典データセット
uspto-grants-2013_04
特許番号
US08415336B2

反応ノート

読み込み中…