p-Toluenesulfonic acid monohydrate → HCID 68645807, compound

HRID 1160675Notes

Reaction equation

HRID 1160675 reaction equation
[O:1]=[C:2]1[CH2:10][CH2:9][CH2:8][C:7]2[N:6]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[CH:5]=[CH:4][C:3]1=2.O.C1(C)C=CC(S(O)(=O)=O)=CC=1>C(OC(C)=C)(=O)C>[O:1]=[C:2]1[CH2:10][CH2:9][CH2:8][C:7]2[N:6]([C:11]([OH:13])=[O:12])[CH:5]=[CH:4][C:3]1=2.[O:1]=[C:2]1[CH2:10][CH2:9][CH2:8][C:7]2[N:6]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[CH:5]=[CH:4][C:3]1=2

Participants

4

Reactant 2

HCID 521998p-Toluenesulfonic acid monohydrateHCID 53439110tert-Butyl 4-oxo-4,5,6,7-tetrahydro-1H-indole-1-carboxylate

Product 1

HCID 68645807HCID 68645807, compound

Reagents, catalysts & solvents 1

HCID 7916Isopropenyl acetateSolvent

Procedure

Tert-butyl 4,5,6,7-tetrahydro-4-oxoindole-1-carboxylate 4,5,6,7-tetrahydro-4-oxoindole-1-carboxylate (1) was prepared using a modified literature procedure (Maekawa, which is hereby incorporated by reference). To a dry 250 mL round bottom flask charged with a magnetic stir bar was added tert-butyl 4,5,6,7-tetrahydro-4-oxoindole-1-carboxylate (4.619 g, 19.6 mmole), 150 mL isopropenyl acetate and p-toluenesulfonic acid monohydrate (67 mg, 0.35 mmole). The solution was refluxed for 5 hours while the solvent was slowly distilled off at the rate of 20 mL/hour. After cooling the solution to ambient temperature, 100 mL of a 1:1 solution of diethyl ether and saturated aqueous NaHCO3 was added. The layers were separated and the aqueous layer extracted with 30 mL diethyl ether. The combined ether extracts were washed with saturated aqueous NaHCO3 (2×30 mL), brine (30 mL), and dried over anhydrous MgSO4. The solution was then filtered through a plug of silica gel and concentrated in vacuo. The residue was purified via flash chromatography (silica gel, 5:1 pentane:diethyl ether) to give the product as a white solid (1.40 g, 26% yield), mp 79-80° C.; Rf 0.26 (5:1 pentane:diethyl ether); FTIR (neat): 2978, 1736 cm−1; 1H NMR (500 MHz, CDCl3) δ 7.09 (d, J=3.5 Hz, 1H), 5.95 (d, J=3.5 Hz, 1H), 5.24 (t, J=4.5 Hz, 1H), 3.10 (t, J=9.5 Hz, 2H), 2.56 (dt, J=9.5, 4.5 Hz, 2H), 2.23 (s, 3H), 1.58 (s, 9H); 13C NMR (75 MHz, CDCl3) δ 169.1 (C), 149.0 (C), 143.3 (C), 130.8 (C), 119.9 (CH), 118.9 (C), 106.8 (CH), 105.4 (CH), 83.8 (C), 27.9 (CH3), 23.1 (CH2), 21.7 (CH2), 20.7 (CH3); LCMS (ESI) m/z (relative intensity): 250.0 (100), 236.0 (90); HRMS (EI) Calcd for C15H19NO4 277.1309, Found 277.1309.

Workup

  1. additionTo a dry 250 mL round bottom flask charged with a magnetic stir bar
  2. temperatureThe solution was refluxed for 5 hours while the solvent
  3. distillationwas slowly distilled off at the rate of 20 mL/hour
  4. addition100 mL of a 1:1 solution of diethyl ether and saturated aqueous NaHCO3 was added
  5. customThe layers were separated
  6. extractionthe aqueous layer extracted with 30 mL diethyl ether
  7. washThe combined ether extracts were washed with saturated aqueous NaHCO3 (2×30 mL), brine (30 mL)
  8. dry with materialdried over anhydrous MgSO4
  9. filtrationThe solution was then filtered through a plug of silica gel
  10. concentrationconcentrated in vacuo
  11. customThe residue was purified via flash chromatography (silica gel, 5:1 pentane:diethyl ether)

Sources & evidence

ORD record
ord-f9437ef01249443791cbce2f36ea128a
Source dataset
uspto-grants-2010_10
Patent number
US07816536B2

Reaction notes

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