Pyridine → 3-(N-Tosyl-L-alaninyloxy)-1-methyl-5-phenylpyrrole

HRID 236638Notes

Reaction equation

HRID 236638 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.F[C:8](F)(F)[C:9](O)=O.[S:14]([NH:24][C@H:25]([C:27](Cl)=[O:28])[CH3:26])([C:17]1[CH:23]=[CH:22][C:20]([CH3:21])=[CH:19][CH:18]=1)(=[O:16])=[O:15].[CH3:30][CH2:31][CH2:32][CH2:33]CC.CC[O:38]C(C)=O>C1COCC1>[S:14]([NH:24][C@H:25]([C:27]([O:28][C:5]1[CH:4]=[C:3]([C:9]2[CH:8]=[CH:33][CH:32]=[CH:31][CH:30]=2)[N:1]([CH3:2])[CH:6]=1)=[O:38])[CH3:26])([C:17]1[CH:23]=[CH:22][C:20]([CH3:21])=[CH:19][CH:18]=1)(=[O:16])=[O:15]

Participants

6

Reactant 4

HCID 1049PyridineHCID 6422Trifluoroacetic acidHCID 12924680HCID 12924680, compoundHCID 21226206Ethyl acetate hexane

Product 1

HCID 137853323-(N-Tosyl-L-alaninyloxy)-1-methyl-5-phenylpyrrole

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

To a mixture of deoxygenated methanol (15.5 ml) and 3-acetoxy-1-methyl-5-phenylpyrrole (11) (1.3 g, 6.2 mmole), under argon, was added deoxygenated NaOH (2N, 12.5 ml). The reaction mixture was stirred in an ice-bath for 15 minutes. Then deoxygenated citric acid (2M, 7 ml) was added and the resulting mixture was stirred in an ice bath for 8 minutes. The reaction mixture was concentrated under reduced pressure, then 20 ml of water was added and was extracted twice with ethylacetate (EtOAc) (50 ml). The EtOAc layers were combined, dried over MgSO4, filtered and concentrated under reduced pressure to give 3-hydroxy-1-methyl-5-phenylpyrrole (12) as an orange residue. Under argon, a cold solution of anhydrous THF (12.4 ml), pyridine (0.6 ml, 7.4 mmole, 1.2 eq) and trifluoroacetic acid (1.2 ml, 15 mmole, 2.4 eq) was added to the orange residue, followed immediately by the additon of a solution of freshly prepared N-tosyl-L-alaninyl chloride (1.2 g, 7.4 mmole, 1.2 eq) in anhydrous THF (12.4 ml). The resulting mixture was stirred for one hr at 0° C. Then the reaction was quenched by the addition of aqueous citric acid (1M, 5 ml) and EtOAc (30 ml). After a brief mixing, the layers were separated and the organic layer was successively washed with saturated NaCl solution, twice with 5% NaHCO3 solution and again with saturated NaCl solution. The EtOAc extract was then dried over MgSO4, treated with Norit 211, filtered and concentrated under reduced pressure to give the crude product (13) as an orange residue. This was dissolved in hexane:EtOAc (1:1) (5 ml) and chromatographed on a column (SiO2, 100 g) by elution with hexane:EtOAc (7:3) to give 1 g of (13) as a thick light orange oil. A portion of this crude product was further purified by semi-preparative HPLC (column, IBM silica, 1 cm×25 cm; mobile phase, hexane:EtOAc 8:2; flow rate, 4.0 ml/min; pressure, 0.2 psi) to yield a honey color thick oil (13).

Workup

  1. customThen the reaction was quenched by the addition of aqueous citric acid (1M, 5 ml) and EtOAc (30 ml)
  2. customAfter a brief mixing, the layers were separated
  3. washthe organic layer was successively washed with saturated NaCl solution, twice with 5% NaHCO3 solution and again with saturated NaCl solution
  4. extractionThe EtOAc extract
  5. dry with materialwas then dried over MgSO4
  6. additiontreated with Norit 211
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customto give the crude product (13) as an orange residue
  10. customchromatographed on a column (SiO2, 100 g) by elution with hexane:EtOAc (7:3)

Sources & evidence

ORD record
ord-4d1797347aee4f1abc42e733b7b99af0
Source dataset
uspto-grants-1987_02
Patent number
US04645842

Reaction notes

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