1,2-Dihydro-6,7-dimethoxy-3-nitronaphthalene → 5-(1,2,3,4-Tetrahydro-6,7-dimethoxy-2-nitro-1-naphthyl)-2-propyl-4-(((2-tetrahydropyranyl)oxy)methyl)oxazole

HRID 235091Notes

Reaction equation

HRID 235091 reaction equation
C([Li])CCC.Br[C:7]1[O:11][C:10]([CH2:12][CH2:13][CH3:14])=[N:9][C:8]=1[CH2:15][O:16][CH:17]1[CH2:22][CH2:21][CH2:20][CH2:19][O:18]1.[CH3:23][O:24][C:25]1[CH:26]=[C:27]2[C:32](=[CH:33][C:34]=1[O:35][CH3:36])[CH2:31][CH2:30][C:29]([N+:37]([O-:39])=[O:38])=[CH:28]2>C1COCC1>[CH3:36][O:35][C:34]1[CH:33]=[C:32]2[C:27](=[CH:26][C:25]=1[O:24][CH3:23])[CH:28]([C:7]1[O:11][C:10]([CH2:12][CH2:13][CH3:14])=[N:9][C:8]=1[CH2:15][O:16][CH:17]1[CH2:22][CH2:21][CH2:20][CH2:19][O:18]1)[CH:29]([N+:37]([O-:39])=[O:38])[CH2:30][CH2:31]2

Participants

5

Reactant 3

HCID 107522201,2-Dihydro-6,7-dimethoxy-3-nitronaphthaleneHCID 233535735-Bromo-2-propyl-4-(((2-tetrahydropyranyl)oxy)methyl)oxazoleHCID 178418339Butyllithium

Product 1

HCID 233535525-(1,2,3,4-Tetrahydro-6,7-dimethoxy-2-nitro-1-naphthyl)-2-propyl-4-(((2-tetrahydropyranyl)oxy)methyl)oxazoleYield 89%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

n-Butyllithium (2.5M in hexane, 10 mmol) was added to a solution of the compound from step 29c (2.70 g, 8.88 mmol) in 40 mL of THF cooled to -78° C. The resulting yellow solution was stirred for 30 min at -78° C., and a solution of 1,2-dihydro-6,7-dimethoxy-3-nitronaphthalene (2.227 g, 9.48 mmol), from Example 1b, precooled to -78° C., was added via cannula. The reaction was stirred for 2 hours at -78° C., then the reaction was quenched by the addition of 10 mL of satd. NH4Cl. After warming to room temperature, the organic layer was separated, and the aqueous layer was extracted with 2×50 mL of methylene chloride. The organics were combined, dried over MgSO4 and concentrated. The crude product was dissolved in 45 mL of methanol and treated with 8 mL of triethylamine. This solution was stirred for 15 hours at room temperature. The solvent was removed under reduced pressure, and the residue was chromatographed on silica gel, eluting with 30-60% ethyl acetate in hexane, to afford after removal of the solvent and drying, 3.64 g (89% yield) of the title product as an oil. MS: 461 (M+H)+. NMR showed a mixture of diastereomers.

Workup

  1. customprecooled to -78° C.
  2. additionwas added via cannula
  3. stirringThe reaction was stirred for 2 hours at -78° C.
  4. customthe reaction was quenched by the addition of 10 mL of satd
  5. temperatureAfter warming to room temperature
  6. customthe organic layer was separated
  7. extractionthe aqueous layer was extracted with 2×50 mL of methylene chloride
  8. dry with materialdried over MgSO4
  9. concentrationconcentrated
  10. dissolutionThe crude product was dissolved in 45 mL of methanol
  11. additiontreated with 8 mL of triethylamine
  12. stirringThis solution was stirred for 15 hours at room temperature
  13. customThe solvent was removed under reduced pressure
  14. customthe residue was chromatographed on silica gel
  15. washeluting with 30-60% ethyl acetate in hexane
  16. customto afford
  17. customafter removal of the solvent
  18. customdrying

Sources & evidence

ORD record
ord-f9a09cb4c5d744a688ec00dda0a713da
Source dataset
uspto-grants-1997_01
Patent number
US05597832

Reaction notes

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