Methyl 4-hydroxy-3-methoxyphenylacetate → Methyl 2-(3-methoxy-4-(4-nitro-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazol-5-yloxy)phenyl)acetate

HRID 2423310Notes

Reaction equation

HRID 2423310 reaction equation
[CH3:1][O:2][C:3](=[O:14])[CH2:4][C:5]1[CH:10]=[CH:9][C:8]([OH:11])=[C:7]([O:12][CH3:13])[CH:6]=1.[Na].Cl[C:17]1[C:18]([N+:34]([O-:36])=[O:35])=[C:19]2[C:23](=[CH:24][CH:25]=1)[N:22]([CH2:26][O:27][CH2:28][CH2:29][Si:30]([CH3:33])([CH3:32])[CH3:31])[N:21]=[CH:20]2>C1COCC1>[CH3:13][O:12][C:7]1[CH:6]=[C:5]([CH2:4][C:3]([O:2][CH3:1])=[O:14])[CH:10]=[CH:9][C:8]=1[O:11][C:17]1[C:18]([N+:34]([O-:36])=[O:35])=[C:19]2[C:23](=[CH:24][CH:25]=1)[N:22]([CH2:26][O:27][CH2:28][CH2:29][Si:30]([CH3:32])([CH3:33])[CH3:31])[N:21]=[CH:20]2

Participants

5

Reactant 3

HCID 85214Methyl 4-hydroxy-3-methoxyphenylacetateHCID 5360545SodiumHCID 598648595-chloro-4-nitro-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazole

Product 1

HCID 59864798Methyl 2-(3-methoxy-4-(4-nitro-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazol-5-yloxy)phenyl)acetate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

To methyl-3-methoxy-4-hydroxyphenylacetate (0.062 g, 0.32 mmol) in dry THF (5 mL) under nitrogen was added sodium hexamethyldisylazide (1M solution in THF) (312 μl, 0.31 mmol). After 10 min. stirring at room temperature 5-chloro-4-nitro-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazole (93 mg, 0.28 mmol) in 5 mL of THF was added. The resulting mixture was stirred at reflux for 5 days. After that time the mixture was quenched with water and extracted with ethyl acetate (3×25 mL). The combined organic extracts were washed with brine, dried over magnesium sulfate and concentrated under reduced pressure. The desired product was isolated by chromatography (10% ethyl acetate/hexane). 1H NMR (400 MHz) (CDCl3) δ 8.40 (s, 1H); 7.70 (d, J=9.1 Hz, 1H); 7.05 (d, J=9.1 Hz, 1H); 6.95 (m, 2H), 6.84 (dd, J=1.5, 8.0 Hz, 1H); 5.75 (s, 2H); 3.82 (s, 3H), 3.62, s, 3H); 3.62 (s, 2H); 3.57 (t, J=8.0 Hz, 2H); 0.89 (t, J=8.0 Hz, 2H); 0.0 (s, 9H).

Workup

  1. additionwas added
  2. temperatureat reflux for 5 days
  3. customAfter that time the mixture was quenched with water
  4. extractionextracted with ethyl acetate (3×25 mL)
  5. washThe combined organic extracts were washed with brine
  6. dry with materialdried over magnesium sulfate
  7. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-353d28c8e0194bc6a3ca81fd000ec45a
Source dataset
uspto-grants-2011_06
Patent number
US07960567B2

Reaction notes

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