3-Methanesulfonyl-5-(trifluoromethyl)benzoic acid → HCID 70663242, compound

HRID 878342Notes

Reaction equation

HRID 878342 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][N:11]=[CH:10][C:9]=2[NH:14][CH2:15][CH:16]2[CH2:21][CH2:20][CH2:19][O:18][CH2:17]2)=[C:4]([O:22][CH3:23])[CH:3]=1.[CH3:24][S:25]([C:28]1[CH:29]=[C:30]([CH:34]=[C:35]([C:37]([F:40])([F:39])[F:38])[CH:36]=1)[C:31](O)=[O:32])(=[O:27])=[O:26]>>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][N:11]=[CH:10][C:9]=2[N:14]([CH2:15][CH:16]2[CH2:21][CH2:20][CH2:19][O:18][CH2:17]2)[C:31](=[O:32])[C:30]2[CH:34]=[C:35]([C:37]([F:40])([F:38])[F:39])[CH:36]=[C:28]([S:25]([CH3:24])(=[O:27])=[O:26])[CH:29]=2)=[C:4]([O:22][CH3:23])[CH:3]=1

Participants

3

Reactant 2

HCID 215445163-Methanesulfonyl-5-(trifluoromethyl)benzoic acidHCID 70663199HCID 70663199, compound

Product 1

HCID 70663242HCID 70663242, compound

Procedure

The title compound was prepared in analogy to example 90, from 4-(4-fluoro-2-methoxyphenyl)-N-((tetrahydro-2H-pyran-3-yl)methyl)pyridin-3-amine and 3-(methylsulfonyl)-5-(trifluoromethyl)benzoic acid (example 114, intermediate a) after a reaction time of 90 hours at room temperature. The compound was purified by silica gel chromatography on a 20 g column using an MPLC system (CombiFlash Companion, Isco Inc.) eluting with a gradient of n-heptane:EtOAc (100:0 to 0:100). Chiral chromatography on a Ciralpak AD column with a gradient of ethanol (containing 0.05% formic acid): n-heptane (40:60) furnished both enantiomers, with the desired enantiomer eluting second. Colorless solid (19%). MS (ESI): m/z=567.158 [M+H]+.

Workup

  1. customThe compound was purified by silica gel chromatography on a 20 g column
  2. washeluting with a gradient of n-heptane:EtOAc (100:0 to 0:100)
  3. customChiral chromatography on a Ciralpak AD column with a gradient of ethanol (containing 0.05% formic acid): n-heptane (40:60) furnished both enantiomers
  4. washwith the desired enantiomer eluting second

Sources & evidence

ORD record
ord-3b7b743b11df47229d10ed92c6054cfe
Source dataset
uspto-grants-2015_03
Patent number
US08987307B2

Reaction notes

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