Triethylamine → 3-(4-tert-Butoxycarbonyl-piperazine-1-carbonyl)-2-(3-fluoro-2-methyl-benzyl)-1-phenyl-indolizine-7-carboxylic acid methyl ester

HRID 1963056Notes

Reaction equation

HRID 1963056 reaction equation
[F:1][C:2]1[C:3]([CH3:31])=[C:4]([CH:28]=[CH:29][CH:30]=1)[CH2:5][C:6]1[C:7]([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)=[C:8]2[N:13]([C:14]=1[C:15](O)=[O:16])[CH:12]=[CH:11][C:10]([C:18]([O:20][CH3:21])=[O:19])=[CH:9]2.[C:32]([O:36][C:37]([N:39]1[CH2:44][CH2:43][NH:42][CH2:41][CH2:40]1)=[O:38])([CH3:35])([CH3:34])[CH3:33].C(N(CC)CC)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F>CN(C=O)C.[Cl-].[Na+].O.CC(=O)OCC>[CH3:21][O:20][C:18]([C:10]1[CH:11]=[CH:12][N:13]2[C:8]([CH:9]=1)=[C:7]([C:22]1[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=1)[C:6]([CH2:5][C:4]1[CH:28]=[CH:29][CH:30]=[C:2]([F:1])[C:3]=1[CH3:31])=[C:14]2[C:15]([N:42]1[CH2:43][CH2:44][N:39]([C:37]([O:36][C:32]([CH3:35])([CH3:33])[CH3:34])=[O:38])[CH2:40][CH2:41]1)=[O:16])=[O:19]

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 143452tert-Butyl piperazine-1-carboxylateHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 677736342-(3-Fluoro-2-methyl-benzyl)-7-methoxycarbonyl-1-phenyl-indolizine-3-carboxylic acid

Product 1

HCID 706639703-(4-tert-Butoxycarbonyl-piperazine-1-carbonyl)-2-(3-fluoro-2-methyl-benzyl)-1-phenyl-indolizine-7-carboxylic acid methyl esterYield 40.1%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

To a solution of the crude compound obtained in step 4 (0.420 g, 0.69 mmol), 1-tert-butoxycarbonyl-piperazine (0.142 g, 0.76 mmol) and triethylamine (0.48 ml, 2.78 mmol) in 3.5 ml of DMF cooled at 0° C., was added TBTU (0.490 g, 1.53 mmol) in small portions, and the mixture was stirred at room temperature overnight. 10 ml of EA and 20 ml of brine were then added, the aqueous phase was separated and extracted twice with EA. The combined organic phases were washed with water, 1 N hydrochloric acid, water, an saturated solution of sodium hydrogencarbonate and brine, dried over sodium sulfate, filtered and evaporated to dryness under reduced pressure. The residue was purified by chromatography on silica gel (cyclohexane/EA, 100:0, then 70:30) to give 0.162 g of the title compound as a beige solid.

Workup

  1. customthe aqueous phase was separated
  2. extractionextracted twice with EA
  3. washThe combined organic phases were washed with water, 1 N hydrochloric acid, water
  4. dry with materialan saturated solution of sodium hydrogencarbonate and brine, dried over sodium sulfate
  5. filtrationfiltered
  6. customevaporated to dryness under reduced pressure
  7. customThe residue was purified by chromatography on silica gel (cyclohexane/EA, 100:0

Sources & evidence

ORD record
ord-e739ac3bac2c4c96ac144d3ae4fd9ee3
Source dataset
uspto-grants-2013_04
Patent number
US08415336B2

Reaction notes

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