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

HRID 1963064ノート

反応式

HRID 1963064 の反応式
[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][CH:41]=[O:42])=[O:7])([CH3:4])([CH3:3])[CH3:2].P([O-])(O)(O)=[O:44].[Na+].CC(=CC)C.C1COCC1.Cl([O-])=O.[Na+]>C(O)(C)(C)C.[Cl-].[Na+].O.O>[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:26]=[CH:27][CH:28]=[CH:29][CH:30]=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:44])=[O:42])=[O:7])([CH3:3])([CH3:4])[CH3:2]

参加物

9

反応物 5

HCID 8028TetrahydrofuranHCID 105532-Methyl-2-buteneHCID 23668197Sodium ChloriteHCID 23672064Monosodium phosphateHCID 86670666(S)-4-[2-(3-fluoro-2-methyl-benzyl)-1-phenyl-indolizine-3-carbonyl]-2-(2-oxo-ethyl)-piperazine-1-carboxylic acid tert-butyl ester

生成物 1

HCID 70663959{(S)-1-tert-Butoxycarbonyl-4-[2-(3-fluoro-2-methyl-benzyl)-1-phenyl-indolizine-3-carbonyl]-piperazin-2-yl}-acetic acid収率 40.2%

試薬・触媒・溶媒 3

HCID 962Water溶媒HCID 6386tert-Butanol溶媒HCID 57417360Sodium chloride; water溶媒

反応条件

温度
0 °C

実験手順

The compound obtained in step 1 (0.960 g, 1.69 mmol) was suspended in 9.6 ml of tert-butanol and cooled to 0° C. A solution of sodium dihydrogenphosphate (0.607 g, 5.06 mmol) in 2.4 ml or water, a 2 M solution of 2-methyl-but-2-ene in THF (5.06 ml, 10.11 mmol) and sodium chlorite (0.286 g, 2.53 mmol) were then added and the mixture was stirred for 3.75 h. Brine (30 ml) was added and the mixture was extracted three times with EA. The combined organic phases were washed twice with 1 N hydrochloric acid and once with brine, dried over sodium sulfate, filtered and evaporated to dryness. The residue was purified by chromatography on silica gel (DCM/MOH, 100:0, then 96:4) to give 0.398 g of the title compound.

後処理

  1. extractionthe mixture was extracted three times with EA
  2. washThe combined organic phases were washed twice with 1 N hydrochloric acid and once with brine
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. customevaporated to dryness
  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-96c9d69a675d408c9378baa3e0de9b8b
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…