Fluorine → (R)-8-(1-Isopropyl-piperidin-4-yloxy)-4-methyl-2-((R)-4,4,4-trifluoro-3-hydroxy-butyl)-3,4-dihydro-2H-pyrazino[1,2-a]indol-1-one

HRID 2105410Notes

Reaction equation

HRID 2105410 reaction equation
[CH:1]([N:4]1[CH2:9][CH2:8][CH:7]([O:10][C:11]2[CH:19]=[CH:18][C:17]3[N:16]4[C@H:20]([CH3:25])[CH2:21][NH:22][C:23](=[O:24])[C:15]4=[CH:14][C:13]=3[CH:12]=2)[CH2:6][CH2:5]1)([CH3:3])[CH3:2].[H-].[Na+].[F:28][C:29]([F:46])([F:45])[C@H:30]([OH:44])[CH2:31][CH2:32]OS(C1C=CC(C)=CC=1)(=O)=O.FC(F)(F)[C@H](O)CCO.FF>>[CH:1]([N:4]1[CH2:9][CH2:8][CH:7]([O:10][C:11]2[CH:19]=[CH:18][C:17]3[N:16]4[C@H:20]([CH3:25])[CH2:21][N:22]([CH2:32][CH2:31][C@@H:30]([OH:44])[C:29]([F:46])([F:45])[F:28])[C:23](=[O:24])[C:15]4=[CH:14][C:13]=3[CH:12]=2)[CH2:6][CH2:5]1)([CH3:3])[CH3:2]

Participants

6

Reactant 5

HCID 24524FluorineHCID 24758Sodium hydrideHCID 2779068(3R)-4,4,4-Trifluoro-1,3-butanediolHCID 11066443(3R)-4,4,4-trifluoro-1-(4-methylbenzenesulfonate)-1,3-ButanediolHCID 16679612(R)-8-(1-isopropylpiperidin-4-yloxy)-4-methyl-3,4-dihydropyrazino[1,2-a]indol-1(2H)-one

Product 1

HCID 16678930(R)-8-(1-Isopropyl-piperidin-4-yloxy)-4-methyl-2-((R)-4,4,4-trifluoro-3-hydroxy-butyl)-3,4-dihydro-2H-pyrazino[1,2-a]indol-1-oneYield 5%

Procedure

The title compound was synthesized in analogy to example 17, from (R)-8-(1-isopropyl-piperidin-4-yloxy)-4-methyl-3,4-dihydro-2H-pyrazino[1,2-a]indol-1-one (example 8), sodium hydride and (R)-toluene-4-sulfonic acid 4,4,4-trifluoro-3-hydroxy-butyl ester (prepared from commercially available (R)-4,4,4-trifluoro-butane-1,3-diol in analogy to M. Tordeux et. al, J. Fluorine Chem. 20, 301 (1982) and U.S. Pat. No. 5,405,967) to give the desired product as a light yellow oil (5%).

Sources & evidence

ORD record
ord-dc3d5f429f6a4c3d96109c3d61515a2d
Source dataset
uspto-grants-2009_08
Patent number
US07579351B2

Reaction notes

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