Ethyl Acetate → HCID 44621592, compound

HRID 386544Notes

Reaction equation

HRID 386544 reaction equation
[OH:1][CH:2]1[CH2:7][CH2:6][N:5]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:4][CH2:3]1.[H-].[Na+].Cl[C:18]1[C:23]([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)=[N:22][N:21]([CH2:30][C:31]2[CH:36]=[CH:35][C:34]([O:37][CH3:38])=[CH:33][CH:32]=2)[C:20](=[O:39])[CH:19]=1.CCOC(C)=O>C1COCC1.[Cl-].[Na+].O>[C:11]([O:10][C:8]([N:5]1[CH2:4][CH2:3][CH:2]([O:1][C:18]2[C:23]([C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)=[N:22][N:21]([CH2:30][C:31]3[CH:36]=[CH:35][C:34]([O:37][CH3:38])=[CH:33][CH:32]=3)[C:20](=[O:39])[CH:19]=2)[CH2:7][CH2:6]1)=[O:9])([CH3:14])([CH3:13])[CH3:12]

Participants

7

Reactant 4

HCID 8857Ethyl AcetateHCID 24758Sodium hydrideHCID 643502Tert-butyl 4-hydroxypiperidine-1-carboxylateHCID 67072761HCID 67072761, compound

Product 1

HCID 44621592HCID 44621592, compoundYield 56.5%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

To a mixture of tert-butyl 4-hydroxypiperidine-1-carboxylate (121 mg, 0.60 mmol) in THF (3 mL) at room temperature under argon was added NaH (24 mg, 0.60 mmol). After stirring at room temperature under argon for 30 minutes, 5-chloro-2-(4-methoxybenzyl)-6-phenylpyridazin-3(2H)-one (163 mg, 0.50 mmol) was added. The resulting reaction mixture was stirred at room temperature for three days. EtOAc (10 mL) and brine (10 mL) were added to the reaction mixture. Layers were separated. Organic layer were washed with water (15 mL), and brine (15 mL). Organic phase was dried (MgSO4), filtered and concentrated. The crude product was dissolved in a small amount of DCM (˜2 ml) and loaded onto a 40 g ISCO silica gel column which was eluted with a 20 min gradient from 0% to 100% EtOAc/Hexanes. 138.9 mg (56.3%) of tert-butyl-4-(1-(4-methoxybenzyl)-6-oxo-3-phenyl-1,6-dihydropyridazin-4-yloxy)piperidine-1-carboxylate was obtained as a white solid. 1H NMR (400 MHz, CDCl3) δ ppm 1.43 (s, 9H) 1.62-1.82 (m, 2H) 1.80-1.98 (m, 2H) 3.16-3.57 (m, J=5.27, 5.27 Hz, 4H) 3.76 (s, 1H) 4.35-4.64 (m, 1H) 5.26 (s, 2H) 6.21 (s, 1H) 6.84 (d, J=8.79 Hz, 2H) 7.33-7.53 (m, 5H) 7.64 (dd, J=6.81, 3.30 Hz, 2H). MS (ESI) 492 (M+H).

Workup

  1. customThe resulting reaction mixture
  2. stirringwas stirred at room temperature for three days
  3. customLayers were separated
  4. washOrganic layer were washed with water (15 mL), and brine (15 mL)
  5. dry with materialOrganic phase was dried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. dissolutionThe crude product was dissolved in a small amount of DCM (˜2 ml)
  9. washwas eluted with a 20 min gradient from 0% to 100% EtOAc/Hexanes

Sources & evidence

ORD record
ord-5a229172632442a98f21df328887c4f8
Source dataset
uspto-grants-2013_02
Patent number
US08372837B2

Reaction notes

Loading…