Hydrochloric Acid → HCID 178448420, compound

HRID 1028174Notes

Reaction equation

HRID 1028174 reaction equation
O=[C:2]1[CH2:7][O:6][CH2:5][C:4]([O-:8])=[CH:3]1.[Na+].[CH2:10]([NH:14][C:15]([NH2:17])=[S:16])[CH2:11][CH2:12][CH3:13].Cl.[Cl:19][C:20]1[CH:21]=[CH:22][C:23]([O:29][CH3:30])=[C:24]([CH:28]=1)[C:25](O)=[O:26].CCN=C=NCCCN(C)C.Cl.ON1C2C=CC=CC=2N=N1.C(N(CC)CC)C>O1CCCC1.C(OCC)(=O)C.CS(C)=O>[CH2:10]([N:14]1[C:2]2[CH2:7][O:6][CH2:5][C:4](=[O:8])[C:3]=2[S:16]/[C:15]/1=[N:17]\[C:25](=[O:26])[C:24]1[CH:28]=[C:20]([Cl:19])[CH:21]=[CH:22][C:23]=1[O:29][CH3:30])[CH2:11][CH2:12][CH3:13]

Participants

11

Reactant 7

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 769705-Chloro-o-anisic acidHCID 1551919Thiourea, butyl-HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 66851893HCID 66851893, compound

Product 1

HCID 178448420HCID 178448420, compoundYield 10.4%

Reagents, catalysts & solvents 3

HCID 679Dimethyl SulfoxideSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent2×

Conditions

Temperature
40 °C

Procedure

To a mixture of sodium 5-oxo-5,6-dihydro-2H-pyran-3-olate (Wenke et al. J. Org. Chem. 2006, 71, 1725-1727) (1.36 g, 10.0 mmol) and n-butylthiourea (Trans World) (1.32 g, 10.0 mmol) in tetrahydrofuran (15 mL) was added a mixture of DMSO (2.1 mL) and 12 N HCl (2.5 mL). The reaction mixture was heated at 40° C. overnight and cooled. The mixture was diluted with ethyl acetate and washed with aqueous sodium bicarbonate. The organic extract was dried (MgSO4), filtered and concentrated. The residue was dried under vacuum for 12 hours and dissolved in tetrahydrofuran (40 mL). To the solution was added 5-chloro-2-methoxy-benzoic acid (1.86 g, 10.0 mmol), N-(3-dimethylaminopropyl)-N-ethylcarbodimide hydrochloride (1.91 g, 10.0 mmol), 1-hydroxybenzotriazole (1.35 g, 10.0 mmol) and triethylamine (3.5 mL, 3.5 mmol). The mixture was stirred overnight at 80° C., then cooled to room temperature. The mixture was diluted with ethyl acetate, washed with 1 M aqueous NaHCO3, dried (Na2SO4), filtered and concentrated. The residue was purified by flash chromatography using an Analogix® IT280™ (SiO2, 0-75% ethyl acetate in hexanes) to afford 412 mg of the title compound. 1H NMR (300 MHz, CDCl3) δ ppm 1.03 (t, J=7.46 Hz, 3H) 1.38-1.52 (m, 2H) 1.77-1.90 (m, 2H) 3.93 (s, 3H) 4.16 (t, J=7.46 Hz, 2H) 4.32 (s, 2H) 4.90 (s, 2H) 6.94 (d, J=8.82 Hz, 1H) 7.40 (dd, J=8.99, 2.88 Hz, 1H) 8.11 (d, J=2.71 Hz, 1H); MS (ESI+) m/z 395 (M+H)+.

Workup

  1. additionwas added
  2. temperaturecooled
  3. washwashed with aqueous sodium bicarbonate
  4. extractionThe organic extract
  5. dry with materialwas dried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was dried under vacuum for 12 hours
  9. dissolutiondissolved in tetrahydrofuran (40 mL)
  10. temperaturecooled to room temperature
  11. washwashed with 1 M aqueous NaHCO3
  12. dry with materialdried (Na2SO4)
  13. filtrationfiltered
  14. concentrationconcentrated
  15. customThe residue was purified by flash chromatography

Sources & evidence

ORD record
ord-a5ecac59e4a14f7884f1ecf07ce6f25b
Source dataset
uspto-grants-2014_05
Patent number
US08735434B2

Reaction notes

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