Tetrahydrofuran → 2-(3-Fluoro-2-methyl-benzyl)-7-methoxycarbonyl-1-phenyl-indolizine-3-carboxylic acid

HRID 1963055Notes

Reaction equation

HRID 1963055 reaction equation
[CH3:1][O:2][C:3]([C:5]1[CH:6]=[CH:7][N:8]2[C:12]([CH:13]=1)=[C:11]([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)[C:10]([CH2:20][C:21]1[CH:26]=[CH:25][CH:24]=[C:23]([F:27])[C:22]=1[CH3:28])=[C:9]2[CH:29]=[O:30])=[O:4].P([O-])(O)(O)=[O:32].[Na+].CC(=CC)C.C1COCC1.Cl([O-])=O.[Na+]>C(O)(C)(C)C.O.[Cl-].[Na+].O.CC(=O)OCC>[F:27][C:23]1[C:22]([CH3:28])=[C:21]([CH:26]=[CH:25][CH:24]=1)[CH2:20][C:10]1[C:11]([C:14]2[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=2)=[C:12]2[N:8]([C:9]=1[C:29]([OH:32])=[O:30])[CH:7]=[CH:6][C:5]([C:3]([O:2][CH3:1])=[O:4])=[CH:13]2

Participants

10

Reactant 5

HCID 8028Tetrahydrofuran2×HCID 105532-Methyl-2-butene2×HCID 23668197Sodium Chlorite2×HCID 23672064Monosodium phosphate2×HCID 88414465Methyl-2-(3-fluoro-2-methyl-benzyl)-3-formyl-1-phenyl-indolizine-7-carboxylate

Product 1

HCID 677736342-(3-Fluoro-2-methyl-benzyl)-7-methoxycarbonyl-1-phenyl-indolizine-3-carboxylic acidYield 137.8%

Reagents, catalysts & solvents 4

HCID 962WaterSolvent2×HCID 6386tert-ButanolSolventHCID 8857Ethyl AcetateSolventHCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
0 °C

Procedure

The compound of step 3 (0.293 g, 0.73 mmol) was suspended in 4 ml of tert-butanol and cooled to 0° C. To this suspension were added a solution of sodium dihydrogenphosphate (0.263 g, 2.19 mmol) in 1 ml of water, a 2 M solution of 2-methyl-2-butene in THF (2.19 ml, 4.38 mmol) and sodium chlorite (0.124 g, 1.09 mmol) in small portions. After stirring at room temperature for 18 h, once more a solution of sodium dihydrogenphosphate (0.263 g, 2.19 mmol) in 2 ml water, a 2 M solution of 2-methyl-2-butene in THF (2.19 ml, 4.38 mmol) and sodium chlorite (0.124 g, 1.09 mmol) were added again and stirring was continued for an additional 48 h. Then 30 ml of a 1:1 mixture of brine and EA were added, the organic phase was separated, and the aqueous phase was extracted with EA. The combined organic phases were washed with brine, dried over sodium sulfate, filtered and evaporated to dryness under reduced pressure to give 0.420 g of the crude title compound as a yellow powder which was directly used in the next step.

Workup

  1. stirringstirring
  2. waitwas continued for an additional 48 h
  3. additionwere added
  4. customthe organic phase was separated
  5. extractionthe aqueous phase was extracted with EA
  6. washThe combined organic phases were washed with brine
  7. dry with materialdried over sodium sulfate
  8. filtrationfiltered
  9. customevaporated to dryness under reduced pressure

Sources & evidence

ORD record
ord-643d0edd8be345d5b361a10ea6d4241e
Source dataset
uspto-grants-2013_04
Patent number
US08415336B2

Reaction notes

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