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

HRID 1963064노트

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HRID 1963064 반응식
[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]

참가 물질

9

반응물 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

생성물 1

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

시약·촉매·용매 3

HCID 962Water용매HCID 6386tert-Butanol용매HCID 57417360Sodium chloride; water용매

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온도
0 °C

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-96c9d69a675d408c9378baa3e0de9b8b
출처 데이터셋
uspto-grants-2013_04
특허 번호
US08415336B2

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