Water → HCID 21309138, compound

HRID 442764Notes

Reaction equation

HRID 442764 reaction equation
O.S(=O)(=O)(O)O.C1([O:12][C:13]2[CH:14]=[C:15]([C@@H:21]([C:29]3[CH:30]=[C:31]([CH:33]=[CH:34][CH:35]=3)[NH2:32])[CH2:22][C:23]3[CH:28]=[CH:27][N:26]=[CH:25][CH:24]=3)[CH:16]=[CH:17][C:18]=2[O:19][CH3:20])CCCC1>O1CCOCC1>[OH:12][C:13]1[CH:14]=[C:15]([C@@H:21]([C:29]2[CH:30]=[C:31]([CH:33]=[CH:34][CH:35]=2)[NH2:32])[CH2:22][C:23]2[CH:28]=[CH:27][N:26]=[CH:25][CH:24]=2)[CH:16]=[CH:17][C:18]=1[O:19][CH3:20]

Participants

5

Reactant 3

HCID 962WaterHCID 1118Sulfuric AcidHCID 18664801HCID 18664801, compound

Product 1

HCID 21309138HCID 21309138, compoundYield 91%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

Water (25 ml) and sulphuric acid (40 ml, concentrated) was added to a solution of 3-[1-(R)-(3-cyclopentyloxy-4-methoxyphenyl)-2-(4-pyridyl)ethyl]aniline (3.8 g, 9.8 mmol prepared as described in International Patent specification No. WO95/17386) in 1,4-dioxane (50 ml) at RT. The mixture was heated at 90° C. for 1 h, cooled and concentrated in vacuo. The pH of the residue was adjusted to pH 8.0-8.5 by the addition of solid NaOH. The mixture was diluted with ethyl acetate (100 ml) and water (50 ml) and extracted with ethyl acetate (2×50 ml). The extract was washed with water (100 ml), brine (100 ml), dried (MgSO4), filtered and concentrated in vacuo to give a crude product which was washed with ethyl acetate to afford 3-[1-(R)-(3-hydroxy-4-methoxyphenyl)-2-(4-pyridyl)ethyl]aniline (Intermediate 1) as a pale yellow powder (2.84 g, 91%). (Found: C, 73.83; H, 6.44; N, 8.09. C20H20N2O2 +0.25 mol. eqv. of ethyl acetate requires C, 73.66; H, 6.48; N, 8.18%), δH (d4 -methanol) 3.3 (2H, d, J 8.0 Hz), 3.77 (3H, s), 4.06 (1H, t, J 8.0 Hz), 6.5 (1H, d, J 2.2 Hz), 6.53-6.78 (5H, m), 6.97 (1H, t, J 7.7 Hz), 7.13 (2H, d, J 5.8 Hz), and 8.25 (2H, d, J 5.6 Hz). m/z (ESI--MH+ 321 (25), 228 (100).

Workup

  1. temperaturecooled
  2. concentrationconcentrated in vacuo
  3. additionThe pH of the residue was adjusted to pH 8.0-8.5 by the addition of solid NaOH
  4. additionThe mixture was diluted with ethyl acetate (100 ml) and water (50 ml)
  5. extractionextracted with ethyl acetate (2×50 ml)
  6. washThe extract was washed with water (100 ml), brine (100 ml)
  7. dry with materialdried (MgSO4)
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customto give a crude product which
  11. washwas washed with ethyl acetate

Sources & evidence

ORD record
ord-d0a312f1d1104261b13f42f8f01d5ae1
Source dataset
uspto-grants-1999_04
Patent number
US05891896

Reaction notes

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