Tetrabutylammonium Fluoride → Tert-butyl 4-(1-methyl-2-oxo-8-(trifluoromethyl)-1,2,3,5-tetrahydrobenzo[5,6][1,4]oxazino[3,4-c][1,2,4]triazin-9-yl)piperidine-1-carboxylate

HRID 519100Notes

Reaction equation

HRID 519100 reaction equation
[CH3:1][CH:2]1[C:7](=[O:8])[N:6](COCC[Si](C)(C)C)[N:5]=[C:4]2[CH2:17][O:18][C:19]3[CH:24]=[C:23]([C:25]([F:28])([F:27])[F:26])[C:22]([CH:29]4[CH2:34][CH2:33][N:32]([C:35]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:36])[CH2:31][CH2:30]4)=[CH:21][C:20]=3[N:3]12.CCCC[N+](CCCC)(CCCC)CCCC.[F-]>C1COCC1>[CH3:1][CH:2]1[C:7](=[O:8])[NH:6][N:5]=[C:4]2[CH2:17][O:18][C:19]3[CH:24]=[C:23]([C:25]([F:26])([F:28])[F:27])[C:22]([CH:29]4[CH2:34][CH2:33][N:32]([C:35]([O:37][C:38]([CH3:39])([CH3:41])[CH3:40])=[O:36])[CH2:31][CH2:30]4)=[CH:21][C:20]=3[N:3]12

Participants

4

Reactant 2

HCID 2724141Tetrabutylammonium FluorideHCID 86727471Tert-butyl 4-(1-methyl-2-oxo-8-(trifluoromethyl)-3-((2-(trimethylsilyl)ethoxy)methyl)-1,2,3,5-tetrahydrobenzo[5,6][1,4]oxazino[3,4-c][1,2,4]triazin-9-yl)piperidine-1-carboxylate

Product 1

HCID 86727472Tert-butyl 4-(1-methyl-2-oxo-8-(trifluoromethyl)-1,2,3,5-tetrahydrobenzo[5,6][1,4]oxazino[3,4-c][1,2,4]triazin-9-yl)piperidine-1-carboxylateYield 73%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of tert-butyl 4-(1-methyl-2-oxo-8-(trifluoromethyl)-3-((2-(trimethylsilyl)ethoxy)methyl)-1,2,3,5-tetrahydrobenzo[5,6][1,4]oxazino[3,4-c][1,2,4]triazin-9-yl)piperidine-1-carboxylate (0.07 g, 0.117 mmol) in THF (2 mL) was added a solution of TBAF in THF (1M, 0.58 mL, 0.585 mmol) and the reaction mixture was heated at reflux for 24 h. The reaction mixture was cooled to rt and the solvent was removed in vacuo. The residue was purified by preparative HPLC (Table 3, Method 23) to give tert-butyl 4-(1-methyl-2-oxo-8-(trifluoromethyl)-1,2,3,5-tetrahydrobenzo[5,6][1,4]oxazino[3,4-c][1,2,4]triazin-9-yl)piperidine-1-carboxylate (0.04 g, 73%). LC/MS (Table 1, Method 3) Rt=1.665 min; MS m/z: 469 [M+H]+.

Workup

  1. temperaturethe reaction mixture was heated
  2. temperatureat reflux for 24 h
  3. customthe solvent was removed in vacuo
  4. customThe residue was purified by preparative HPLC (Table 3, Method 23)

Sources & evidence

ORD record
ord-f49f0cf1bbf740e5a336d4560b09662d
Source dataset
uspto-grants-2015_08
Patent number
US09115151B2

Reaction notes

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