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

HRID 1963064Notes

Reaction equation

HRID 1963064 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][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]

Participants

9

Reactant 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

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 40.2%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6386tert-ButanolSolventHCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
0 °C

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-96c9d69a675d408c9378baa3e0de9b8b
Source dataset
uspto-grants-2013_04
Patent number
US08415336B2

Reaction notes

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