Hydrochloric Acid → 1-[6-(5-{1-[3-Chloro-4-(methylsulfonyl)phenyl]-2-(tetrahydro-2h-pyran-4-yl)ethyl}-1h-pyrrol-2-yl)pyridin-3-yl]ethane-1,2-diol

HRID 1882009Notes

Reaction equation

HRID 1882009 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:12]([CH2:32][CH:33]2[CH2:38][CH2:37][O:36][CH2:35][CH2:34]2)[C:13](=O)[CH2:14][CH2:15][C:16]([C:18]2[CH:23]=[CH:22][C:21]([CH:24]3[CH2:28][O:27]C(C)(C)[O:25]3)=[CH:20][N:19]=2)=O)[CH:5]=[CH:6][C:7]=1[S:8]([CH3:11])(=[O:10])=[O:9].C([O-])(=O)C.[NH4+:43].Cl>C(O)(=O)C.C(OCC)(=O)C.O1CCCC1>[Cl:1][C:2]1[CH:3]=[C:4]([CH:12]([C:13]2[NH:43][C:16]([C:18]3[N:19]=[CH:20][C:21]([CH:24]([OH:25])[CH2:28][OH:27])=[CH:22][CH:23]=3)=[CH:15][CH:14]=2)[CH2:32][CH:33]2[CH2:34][CH2:35][O:36][CH2:37][CH2:38]2)[CH:5]=[CH:6][C:7]=1[S:8]([CH3:11])(=[O:9])=[O:10]

Participants

7

Reactant 3

HCID 313Hydrochloric AcidHCID 517165Ammonium AcetateHCID 593316195-[3-chloro-4-(methylsulfonyl)phenyl]-1-[5-(2,2-dimethyl-1,3-dioxolan-4-yl)pyridin-2-yl]-6-(tetrahydro-2H-pyran-4-yl)hexane-1,4-dione

Product 1

HCID 251071651-[6-(5-{1-[3-Chloro-4-(methylsulfonyl)phenyl]-2-(tetrahydro-2h-pyran-4-yl)ethyl}-1h-pyrrol-2-yl)pyridin-3-yl]ethane-1,2-diolYield 90.1%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent2×

Conditions

Temperature
110 °C

Procedure

To a solution of 5-[3-chloro-4-(methylsulfonyl)phenyl]-1-[5-(2,2-dimethyl-1,3-dioxolan-4-yl)pyridin-2-yl]-6-(tetrahydro-2H-pyran-4-yl)hexane-1,4-dione (620 mg) in acetic acid (5 mL) was added ammonium acetate (1.36 g), and the mixture was stirred at 110° C. for 45 min. After cooling to room temperature, the reaction mixture was diluted with ethyl acetate and washed with water. The ethyl acetate layer was washed with saturated aqueous sodium hydrogen carbonate and saturated brine, dried (MgSO4) and concentrated to give a crude product (660 mg). To a solution of the obtained crude product (660 mg) in tetrahydrofuran (5 mL) was added 1M hydrochloric acid (5 mL), and the mixture was stirred at 50° C. for 3 hr. The reaction mixture was diluted with ethyl acetate, and washed with saturated aqueous sodium hydrogen carbonate. The ethyl acetate layer was washed with saturated brine, dried (MgSO4) and concentrated. The residue was subjected to silica gel column chromatography, and the title compound (500 mg, yield 90%) was obtained as a pale-yellow amorphous solid from a fraction eluted with ethyl acetate-methanol (9:1, volume ratio). MS: 507 (MH+). 1H NMR (300 MHz, CDCl3) δ1.24-1.48 (3H, m), 1.51-1.62 (3 H, m), 1.74-1.89 (1 H, m), 1.95-2.09 (1H, m), 2.38 (1 H, brs), 3.01 (1 H, s), 3.19-3.34 (5 H, m), 3.55-3.66 (1 H, m), 3.69-3.80 (1 H, m), 3.85-3.97 (2H, m), 4.02-4.14 (1 H, m), 4.78 (1 H, dd, J=7.8, 3.6 Hz), 6.61-6.68 (1 H, m), 7.24 (1 H, dd, J=8.1, 1.7 Hz), 7.32 (1 H, d, J=1.5 Hz), 7.50 (1 H, d, J=8.3 Hz), 7.59-7.67 (1 H, m), 7.97-8.05 (1 H, m), 8.30 (1 H, s), 9.71 (1 H, brs).

Workup

  1. temperatureAfter cooling to room temperature
  2. washwashed with water
  3. washThe ethyl acetate layer was washed with saturated aqueous sodium hydrogen carbonate and saturated brine
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated
  6. customto give a crude product (660 mg)
  7. stirringthe mixture was stirred at 50° C. for 3 hr
  8. washwashed with saturated aqueous sodium hydrogen carbonate
  9. washThe ethyl acetate layer was washed with saturated brine
  10. dry with materialdried (MgSO4)
  11. concentrationconcentrated

Sources & evidence

ORD record
ord-e4029411fbee4c25a01db16b8c1b9524
Source dataset
uspto-grants-2012_11
Patent number
US08318746B2

Reaction notes

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