Tetrabutylammonium Fluoride → (R)-tert-butyl 3-methyl-3-((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)amino)azetidine-1-carboxylate

HRID 519057Notes

Reaction equation

HRID 519057 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:11][C:10]([CH3:41])([NH:12][C:13]2[CH:14]=[C:15]3[C:24](=[CH:25][C:26]=2[C:27]([F:30])([F:29])[F:28])[O:23][CH2:22][C:21]2[N:16]3[CH:17]([CH3:40])[C:18](=[O:39])[N:19](COCC[Si](C)(C)C)[N:20]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].CCCC[N+](CCCC)(CCCC)CCCC.[F-]>C1COCC1>[CH3:41][C:10]1([NH:12][C:13]2[C:26]([C:27]([F:28])([F:29])[F:30])=[CH:25][C:24]3[O:23][CH2:22][C:21]4=[N:20][NH:19][C:18](=[O:39])[C@@H:17]([CH3:40])[N:16]4[C:15]=3[CH:14]=2)[CH2:9][N:8]([C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])[CH2:11]1

Participants

4

Reactant 2

HCID 2724141Tetrabutylammonium FluorideHCID 867273933-Methyl-3-[4-methyl-3-oxo-7-trifluoromethyl-2-(2-trimethylsilanyl-ethoxymethyl)-2,3,4,10-tetrahydro-9-oxa-1,2,4a-triaza-phenanthren-6-ylamino]-azetidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 86727421(R)-tert-butyl 3-methyl-3-((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)amino)azetidine-1-carboxylateYield 19.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of 3-methyl-3-[4-methyl-3-oxo-7-trifluoromethyl-2-(2-trimethylsilanyl-ethoxymethyl)-2,3,4,10-tetrahydro-9-oxa-1,2,4a-triaza-phenanthren-6-ylamino]-azetidine-1-carboxylic acid tert-butyl ester (4 g, 6.67 mmol) in THF (10 mL) was added a solution of TBAF (1M in THF, 80 mL, 80 mmol) The reaction mixture was heated at 80° C. for 15 h. The reaction mixture was cooled to ambient temperature and solvent was removed in vacuo. The residue was purified by preparative HPLC (Table 3, Method 17) and further separated by chiral SFC (Table 2, Method 10) to give (R)-tert-butyl 3-methyl-3-((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)amino)azetidine-1-carboxylate (Enantiomer 1, SFC (Table 1, Method 16) Rt: 6.686 min, 0.600 g, 19%) as a white solid, LC/MS (Table 1, Method 2) Rt=1.192 min.; MS m/z: 492 [M+23]+.

Workup

  1. temperatureThe reaction mixture was cooled to ambient temperature
  2. customsolvent was removed in vacuo
  3. customThe residue was purified by preparative HPLC (Table 3, Method 17)
  4. customfurther separated by chiral SFC (Table 2, Method 10)

Sources & evidence

ORD record
ord-143002f9ad3c497fa25e33a0f492740d
Source dataset
uspto-grants-2015_08
Patent number
US09115151B2

Reaction notes

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