Sodium hydride → HCID 22258882, compound

HRID 412320Notes

Reaction equation

HRID 412320 reaction equation
[H-].[Na+].[C:3]([CH2:5][C:6]([O:8][C:9]([CH3:12])([CH3:11])[CH3:10])=[O:7])#[N:4].[CH:13]1([CH2:16][O:17][C:18]2[CH:23]=[CH:22][CH:21]=[C:20]([O:24][CH2:25][C:26]3[CH:31]=[CH:30][C:29]([O:32][CH3:33])=[CH:28][CH:27]=3)[C:19]=2[C:34](=O)[CH:35]=[C:36](SC)[S:37][CH3:38])[CH2:15][CH2:14]1.C1OCCOC2C(=CC=CC=2)OCCOCCOC2C(=CC=CC=2)OC1.C([O-])(=O)C.[NH4+:72]>C1COCC1.C(O)(=O)C>[NH2:4][C:3]1[N:72]=[C:34]([C:19]2[C:20]([O:24][CH2:25][C:26]3[CH:31]=[CH:30][C:29]([O:32][CH3:33])=[CH:28][CH:27]=3)=[CH:21][CH:22]=[CH:23][C:18]=2[O:17][CH2:16][CH:13]2[CH2:15][CH2:14]2)[CH:35]=[C:36]([S:37][CH3:38])[C:5]=1[C:6]([O:8][C:9]([CH3:12])([CH3:11])[CH3:10])=[O:7]

Participants

8

Reactant 5

HCID 24758Sodium hydrideHCID 26541Dibenzo-18-crown-6HCID 70693tert-Butyl cyanoacetateHCID 517165Ammonium AcetateHCID 22258817HCID 22258817, compound

Product 1

HCID 22258882HCID 22258882, compoundYield 29.2%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

To a suspension of NaH (60%, 0.056 g, 1.39 mmol) in TBF (3 mL) was added a solution of t-butyl cyanoacetate (0.197 g, 1.392 mmol) in THF (1 mL) in one portion. After 10 min, a solution of 1-{2-(cyclopropylmethoxy)-6-[(4-methoxybenzyl)-oxy]phenyl}-3,3-bis(methylsulfanyl)-2-propene-1-one (0.500 g, 1.16 mmol) in THF (3 mL) was added followed by dibenzo-18-crown-6 (0.013 g, 0.035 mmol). The resulting mixture was refluxed for 4 hrs. After cooled to room temperature, the mixture was partitioned between 0.1 N acetic acid solution and CH2Cl2. The organic phase was separated, dried over Na2SO4, filtered, and concentrated under reduced pressure. The residual oil was dissolved in 1,2-dichloroethane (1 mL) and acetic acid (1 mL), and ammonium acetate (1.20 g, 15.57 mmol) was added. The mixture was stirred at 120° C. for 0.5 hrs. After cooled to room temperature, the mixture was partitioned between ethyl acetate and saturated aqueous NaHCO3 solution. The organic phase was washed with saturated aqueous NaHCO3 solution and brine, dried over Na2SO4, filtered, and concentrated under reduced pressure. Purification by column chromatography on silica gel (hexane/ethyl acetate 4:1 to 3:1) gave tert-butyl 2-amino-6-{2-(cyclopropylmethoxy)-6-[(4-methoxybenzyl)oxy]phenyl}-4-(methyl-sulfanyl)nicotinate as an pale yellow oil (0.177 g, yield; 29%).

Workup

  1. temperatureThe resulting mixture was refluxed for 4 hrs
  2. customthe mixture was partitioned between 0.1 N acetic acid solution and CH2Cl2
  3. customThe organic phase was separated
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. dissolutionThe residual oil was dissolved in 1,2-dichloroethane (1 mL)
  8. temperatureAfter cooled to room temperature
  9. customthe mixture was partitioned between ethyl acetate and saturated aqueous NaHCO3 solution
  10. washThe organic phase was washed with saturated aqueous NaHCO3 solution and brine
  11. dry with materialdried over Na2SO4
  12. filtrationfiltered
  13. concentrationconcentrated under reduced pressure
  14. customPurification by column chromatography on silica gel (hexane/ethyl acetate 4:1 to 3:1)

Sources & evidence

ORD record
ord-c2d53980e3e244868541ad4c6d889dba
Source dataset
uspto-grants-2003_05
Patent number
US06562811B1

Reaction notes

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