Trifluoroacetic acid → 8-(((Tert-butyldiphenylsilyl)oxy)methyl)-1-isopropyl-7-(methylsulfonyl)-3,4-dihydropyrazino[1,2-a]indole

HRID 1521502Notes

Reaction equation

HRID 1521502 reaction equation
[Si:1]([O:18][CH2:19][C:20]1[CH:21]=[C:22]2[C:26](=[CH:27][C:28]=1[S:29]([CH3:32])(=[O:31])=[O:30])[N:25]([CH2:33][CH2:34][NH:35]C(=O)OC(C)(C)C)[C:24]([C:43](=O)[CH:44]([CH3:46])[CH3:45])=[CH:23]2)([C:14]([CH3:17])([CH3:16])[CH3:15])([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.FC(F)(F)C(O)=O>C(Cl)Cl>[Si:1]([O:18][CH2:19][C:20]1[C:28]([S:29]([CH3:32])(=[O:31])=[O:30])=[CH:27][C:26]2[N:25]3[CH2:33][CH2:34][N:35]=[C:43]([CH:44]([CH3:45])[CH3:46])[C:24]3=[CH:23][C:22]=2[CH:21]=1)([C:14]([CH3:16])([CH3:15])[CH3:17])([C:8]1[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 131732710tert-butyl(2-(5-(((tert-butyldiphenylsilyl)oxy)methyl)-2-isobutyryl-6-(methylsulfonyl)-1H-indol-1-yl)ethyl)carbamate

Product 1

HCID 898159918-(((Tert-butyldiphenylsilyl)oxy)methyl)-1-isopropyl-7-(methylsulfonyl)-3,4-dihydropyrazino[1,2-a]indoleYield 65.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of tert-butyl (2-(5-(((tert-butyldiphenylsilyl)oxy)methyl)-2-isobutyryl-6-(methylsulfonyl)-1H-indol-1-yl)ethyl)carbamate (250 mg, 0.37 mmol) in CH2Cl2 (5.0 mL) was added trifluoroacetic acid (1.0 mL) and the mixture was allowed to stir at rt for 1 h. The excess amount of TFA was removed by azeotropic evaporation with toluene under reduced pressure. The residue was redissolved in CH2Cl2 (5 mL) and Et3N (0.5 mL) was added. The reaction mixture was stirred at rt for 45 min and concentrated in vacuo. The residue was purified by flash chromatography over silica gel eluting with CH2Cl2/methanol (98/2) to provide 8-(((tert-butyldiphenylsilyl)oxy)methyl)-1-isopropyl-7-(methylsulfonyl)-3,4-dihydropyrazino[1,2-a]indole (135 mg, 65% yield). LC-MS m/z 559 [M+H]+.

Workup

  1. customThe excess amount of TFA was removed by azeotropic evaporation with toluene under reduced pressure
  2. dissolutionThe residue was redissolved in CH2Cl2 (5 mL)
  3. additionEt3N (0.5 mL) was added
  4. stirringThe reaction mixture was stirred at rt for 45 min
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by flash chromatography over silica gel eluting with CH2Cl2/methanol (98/2)

Sources & evidence

ORD record
ord-1d2ee96fa90547319fb2a00b07b02e06
Source dataset
uspto-grants-2015_07
Patent number
US09073931B2

Reaction notes

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