Sodium hydride → 6-Bromo-4-methyl-7-trifluoromethyl-2-(2-trimethylsilanyl-ethoxymethyl)-2,10-dihydro-9-oxa-1,2,4a-triaza-phenanthren-3-one

HRID 518956Notes

Reaction equation

HRID 518956 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]2[C:13](=[CH:14][C:15]=1[C:16]([F:19])([F:18])[F:17])[O:12][CH2:11][C:10]1[N:5]2[CH:6]([CH3:21])[C:7](=[O:20])[NH:8][N:9]=1.[H-].[Na+].Cl[CH2:25][O:26][CH2:27][CH2:28][Si:29]([CH3:32])([CH3:31])[CH3:30]>C1COCC1>[Br:1][C:2]1[CH:3]=[C:4]2[C:13](=[CH:14][C:15]=1[C:16]([F:17])([F:18])[F:19])[O:12][CH2:11][C:10]1[N:5]2[CH:6]([CH3:21])[C:7](=[O:20])[N:8]([CH2:25][O:26][CH2:27][CH2:28][Si:29]([CH3:32])([CH3:31])[CH3:30])[N:9]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 27242712-Chloromethyl 2-(trimethylsilyl)ethyl etherHCID 867273016-Bromo-4-methyl-7-trifluoromethyl-2,10-dihydro-9-oxa-1,2,4a-triaza-phenanthren-3-one

Product 1

HCID 867273036-Bromo-4-methyl-7-trifluoromethyl-2-(2-trimethylsilanyl-ethoxymethyl)-2,10-dihydro-9-oxa-1,2,4a-triaza-phenanthren-3-oneYield 67%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a 0° C. solution of 6-bromo-4-methyl-7-trifluoromethyl-2,10-dihydro-9-oxa-1,2,4a-triaza-phenanthren-3-one (0.364 g, 1.0 mmol) in THF (50 mL) was added sodium hydride (60% in mineral oil, 0.080 g, 2 mmol) and the reaction mixture was stirred for 0.5 h. (2-(chloromethoxy)ethyl)trimethylsilane (0.250 g, 1.5 mmol) was added and the mixture was stirred at ambient temperature for 2 h. The reaction was quenched with water (100 mL) and the aqueous mixture was extracted with EtOAc (2×30 mL). The combined organic layers were washed with brine (30 mL), dried over Na2SO4, filtered and evaporated in vacuo. The residue was purified by column chromatography on silica gel (eluting with 3-20% EtOAc in petroleum ether) to give 6-bromo-4-methyl-7-trifluoromethyl-2-(2-trimethylsilanyl-ethoxymethyl)-2,10-dihydro-9-oxa-1,2,4a-triaza-phenanthren-3-one as a white solid (0.330 g, 67%). 1H NMR (CDCl3, 400 MHz): δ 7.32 (s, 1H), 7.16 (s, 1H), 5.11 (q, J=8.8 Hz, 2H), 4.75 (d, J=12.6 Hz, 1H), 4.69 (q, J=6.4 Hz, 1H), 4.57 (d, J=12.6 Hz, 1H), 3.65 (t, J=8.4 Hz, 2H), 1.51 (d, J=6.8 Hz, 3H), 0.99 (t, J=8.4 Hz, 2H), 0.01 (s, 9H).

Workup

  1. additionwas added
  2. customThe reaction was quenched with water (100 mL)
  3. extractionthe aqueous mixture was extracted with EtOAc (2×30 mL)
  4. washThe combined organic layers were washed with brine (30 mL)
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. customevaporated in vacuo
  8. customThe residue was purified by column chromatography on silica gel (eluting with 3-20% EtOAc in petroleum ether)

Sources & evidence

ORD record
ord-053b9899f3de4a0f862ae38b00529a06
Source dataset
uspto-grants-2015_08
Patent number
US09115151B2

Reaction notes

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