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

HRID 986837Notes

Reaction equation

HRID 986837 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 (5) (1.3 g, 6.2 mmole), under argon, was added deoxygenated NaOH (2N, 12.5 ml). The reaction mixture was stirred in an icebath for 15 minutes. Then deoxygenated citric acid (2M, 7 ml) was added and the resulting mixture was stirred and 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-N-methyl-5-phenylpyrrole (7) 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 addition 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 (8) 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 (8) 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 (8)

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. customwas then dried over MgSo4
  6. additiontreated with Norit 211
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customto give the crude product (8) as an orange residue
  10. customchromatographed on a column (SiO2, 100 g) by elution with hexane:EtOAc (7:3)

Sources & evidence

ORD record
ord-a66857854de4465893e838d2c2a5909b
Source dataset
uspto-grants-1987_12
Patent number
US04716236

Reaction notes

Loading…